Coleen K Cunningham

Publications (36)193.09 Total impact

• Article: Prevalence of Mycobacteremia among HIV-Infected Infants and Children in Northern Tanzania.

  Katherine D Gray, Coleen K Cunningham, Dana C Clifton, Isaac A Afwamba, Godfrey S Mushi, Levina J Msuya, John A Crump, Ann M Buchanan
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  ABSTRACT: Mycobacterium tuberculosis is a common cause of bloodstream infections among HIV-infected adults in sub-Saharan Africa, and is associated with high morbidity and mortality. We found no cases of mycobacteremia among 93 ill, HIV-infected children in northern Tanzania, despite optimization of laboratory methods and selection of patients thought to be at highest risk for disseminated infection.
  The Pediatric Infectious Disease Journal 01/2013; · 3.58 Impact Factor
• Article: Comprehension of a simplified assent form in a vaccine trial for adolescents.

  Sonia Lee, Bill G Kapogiannis, Patricia M Flynn, Bret J Rudy, James Bethel, Sushma Ahmad, Diane Tucker, Sue Ellen Abdalian, Dannie Hoffman, Craig M Wilson, Coleen K Cunningham
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  ABSTRACT: INTRODUCTION: Future HIV vaccine efficacy trials with adolescents will need to ensure that participants comprehend study concepts in order to confer true informed assent. A Hepatitis B vaccine trial with adolescents offers valuable opportunity to test youth understanding of vaccine trial requirements in general. METHODS: Youth reviewed a simplified assent form with study investigators and then completed a comprehension questionnaire. Once enrolled, all youth were tested for HIV and confirmed to be HIV-negative. RESULTS: 123 youth completed the questionnaire (mean age=15 years; 63% male; 70% Hispanic). Overall, only 69 (56%) youth answered all six questions correctly. CONCLUSIONS: Youth enrolled in a Hepatitis B vaccine trial demonstrated variable comprehension of the study design and various methodological concepts, such as treatment group masking.
  Journal of medical ethics 01/2013; · 1.21 Impact Factor
• Article: Utility of rapid antibody tests to exclude HIV-1 infection among infants and children aged <18 months in a low-resource setting.

  Ann M Buchanan, Behzad Nadjm, Ben Amos, George Mtove, David Sifuna, Coleen K Cunningham, John A Crump, Hugh Reyburn
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  ABSTRACT: Excluding HIV infection among infants and young children in resource-poor settings where nucleic acid amplification tests (NAAT) are not routinely available remains a considerable challenge. To assess the performance of two rapid HIV antibody tests (RT) used alone and in parallel for excluding HIV infection among acutely ill infants and children <18 months in comparison to NAAT in a region where maternal HIV prevalence was approximately 7%. Infants and children ≥2<18 months admitted to hospital with an acute febrile illness had two rapid antibody tests in parallel, with single and parallel results subsequently compared against NAAT. HIV prevalence among 1602 enrolled infants was 3.4%. All 1526 infants with 2 negative RT were HIV negative by NAAT. All 46 infants with 2 positive RT were HIV positive by NAAT. The overall specificity of two rapid tests for excluding HIV infection was 99.5%. Sensitivity and specificity were ≥99% and >98%, respectively, across all age brackets ≥2<18 months. Overall sensitivity and specificity for a single RT was 98.2% and 99%, respectively, for Determine, and 85.5% and 99.6%, respectively, for Capillus. In a setting with a maternal HIV prevalence rate of <10%, a single negative RT had excellent specificity and two negative RT performed in parallel had a perfect negative predictive value for HIV infection among acutely ill patients <18 months of age. In this and similar settings, RT could assist with excluding HIV infection with much lower complexity and cost than NAAT.
  Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 08/2012; 55(3):244-9. · 3.12 Impact Factor
• Article: Increased gut microbial translocation in HIV-infected children persists in virologic responders and virologic failures after antiretroviral therapy.

  Sudheesh Pilakka-Kanthikeel, Sharon Huang, Terry Fenton, William Borkowsky, Coleen K Cunningham, Savita Pahwa
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  ABSTRACT: Gut microbial translocation (MT) is considered a major cause of immune activation (IA) and failure of immune reconstitution in HIV infection. This study investigated the relationship of virus replication, IA, CD4 counts and MT in HIV-infected children. Lipopolysaccharide, bacterial 16S ribosomal DNA (16SrDNA) and soluble CD14 (sCD14) levels were determined in prospectively collected, stored plasma samples from the Pediatric AIDS Clinical Trials Group Protocol P338, a 48-week study initiated in 1997 to compare efficacy of dual nucleosides with a ritonavir-containing regimen. Results of MT were correlated with study data for T cell IA, plasma viral load and CD4 counts in 85 HIV-infected children (ages 2-17 years) designated as virologic responders or virologic failures (VF) at week 44 based on a cutoff of 400 HIV RNA copies/mL. Levels of plasma lipopolysaccharide, 16SrDNA and sCD14 were increased in comparison with HIV-uninfected controls and did not decrease at week 44 even in virologic responders. T cell IA was correlated with viral load and sCD14 at entry and with 16SrDNA and sCD14 at week 44 in total patients and in the VF group. Changes in 16SrDNA correlated with changes in IA and negatively with changes in CD4 counts. 16SrDNA was correlated with sCD14 but not with lipopolysaccharide. MT persists after 44 weeks of antiretroviral therapy in VS and VF patients. In VF, 16SrDNA exhibited relationships to monocyte and T cell IA and CD4 counts but not with viral load, suggesting a dominant role for MT in disease pathogenesis in HIV-infected children.
  The Pediatric Infectious Disease Journal 02/2012; 31(6):583-91. · 3.58 Impact Factor
• Article: Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir.

  Deborah Persaud, Katherine Luzuriaga, Carrie Ziemniak, Petronella Muresan, Thomas Greenough, Terry Fenton, Amanda Blackford, Kimberly Ferguson, Natalie Neu, Coleen K Cunningham
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  ABSTRACT: Therapeutic HIV vaccinations may alter the size of the resting memory CD4 T-cell latent HIV reservoir as HIV establishes latency when memory responses are formed, including those toward HIV. Alternatively, latently infected CD4 T cells maybe killed, while exiting the reservoir upon activation. The effect of therapeutic immunization with modified vaccinia Ankara and Fowlpox-based HIV vaccines on the latent reservoir was examined in 19 young adults who were receiving effective antiretroviral therapy. Correlations between size of the reservoir [measured in infectious units per million (IUPM)] resting CD4 T cells and HIV-specific immune responses, including immune activation were examined. Decay of the reservoir was assessed using random-effects model. A modest transient decrease in the size of the reservoir was observed at week 40 [mean -0.31 log(10) IUPM (95% confidence interval: -0.60 to -0.03; P = 0.03] following HIV vaccinations. The estimated half-life (T1/2) of the reservoir during the 40 weeks following vaccination was 9.8 months and statistically different from zero (P = 0.02), but 35.3 months and not different from zero (P = 0.21) over 72 weeks of study. Latent reservoir size at baseline was not correlated with HIV-specific CD4, CD8 responses or immune activation, but became correlated with CD4 IFNγ (r = 0.54, P = 0.02) and IL-2 responses at 6 weeks after immunization (r = 0.48, P = 0.04). Therapeutic HIV vaccinations led to a transient increase in decay of latently infected CD4 T cells. Further studies of therapeutic HIV vaccines may provide important insights into facilitating decay of the latent reservoir.
  AIDS (London, England) 09/2011; 25(18):2227-34. · 4.91 Impact Factor
• Article: Invasive bacterial and fungal infections among hospitalized HIV‐infected and HIV‐uninfected children and infants in northern Tanzania

  John A. Crump, Habib O. Ramadhani, Anne B. Morrissey, Levina J. Msuya, Lan-Yan Yang, Shein-Chung Chow, Susan C. Morpeth, Hugh Reyburn, Boniface N. Njau, Andrea V. Shaw, Helmut C. Diefenthal, John A. Bartlett, John F. Shao, Werner Schimana, Coleen K. Cunningham, Grace D. Kinabo
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  ABSTRACT: Objective  To describe the contribution of paediatric HIV and of HIV co-infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods.Methods  During 1 year, we enrolled consecutively admitted patients aged ≥2 months and <13 years with current or recent fever. All patients underwent standardized clinical history taking, a physical examination and HIV antibody testing; standard aerobic blood cultures and malaria film were also done, and hospital outcome was recorded. Early infant HIV diagnosis by HIV-1 RNA PCR was performed on those aged <18 months. HIV-infected patients also received serum cryptococcal antigen testing and had their CD4-positive T-lymphocyte count and percent determined.Results  A total of 467 patients were enrolled whose median age was 2 years (range 2 months–13 years); Of those patients, 57.2% were female and 12.2% were HIV-infected. Admission clinical diagnosis of HIV disease was made in 10.7% and of malaria in 60.4%. Of blood cultures, 5.8% grew pathogens; of these 25.9% were Salmonella enterica (including 6 Salmonella Typhi) and 22.2%Streptococcus pneumoniae. Plasmodium falciparum was identified on blood film of 1.3%. HIV infection was associated with S. pneumoniae (odds ratio 25.7, 95% CI 2.8, 234.0) bloodstream infection (BSI), but there was no evidence of an association with Escherichia coli or P. falciparum; Salmonella Typhi BSI occurred only among HIV-uninfected participants. The sensitivity and specificity of an admission clinical diagnosis of malaria were 100% and 40.3%; and for an admission diagnosis of bloodstream infection, they were 9.1% and 86.4%, respectively.Conclusion Streptococcus pneumoniae is a leading cause of bloodstream infection among paediatric admissions in Tanzania and is closely associated with HIV infection. Malaria was over-diagnosed clinically, whereas invasive bacterial disease was underestimated. HIV and HIV co-infections contribute to a substantial proportion of paediatric febrile admissions, underscoring the value of routine HIV testing.Objectifs:  Décrire la contribution du VIH pédiatrique et des coinfections VIH à l’admission dans un hôpital à Moshi, en Tanzanie, en utilisant des méthodes contemporaines de laboratoire.Méthodes:  Durant une année, nous avons recruté des patients consécutifs âgés de ≥2 mois et moins de 13 ans admis avec de la fièvre actuelle ou récente. Tous les patients ont subi un relevé standard de l’historique clinique, un examen physique et des tests d’anticorps VIH. Des hémocultures standard en aérobie et des frottis pour la malaria ont également été effectués et les résultats d’hôpital ont été enregistrés. Un diagnostic précoce du VIH infantile par la PCR du RNA du VIH-1 a été réalisé chez les moins de 18 mois. Les patients infectés par le VIH ont également subi le test de l’antigène cryptococcique sérique et le pourcentage des lymphocytes T CD4+ a été déterminé (%CD4).Résultats:  467 patients ont été recrutés dont l’âge médian était de 2 ans (intervalle: 2 mois à 13 ans). 57,2%étaient de sexe féminin et 12,2%étaient infectés par le VIH. Un diagnostic clinique provisoire pour la maladie VIH a été effectué chez 10,7% et pour la malaria chez 60,4% d’entre eux. 5,8% des cultures de sang ont révélé des agents pathogènes dont 25,9% de Salmonella enterica (dont 6 Salmonella typhi) et 22,2% de Streptococcus pneumoniae. Le Plasmodium falciparum a été identifié dans 1,3% des frottis sanguins. L’infection par le VIH était associée à l’infection sanguine par S. pneumoniae (odds ratio = 25,7; IC95%: 2,8–234,0), mais il n’y avait aucune preuve d’une association avec Escherichia coli ou P. falciparum. L’infection sanguine par Salmonella typhi a eu lieu seulement chez les participants non infectés par le VIH. La sensibilité et la spécificité d’un diagnostic clinique provisoire de la malaria étaient de 100% et 40,3% et pour un diagnostic à l’admission de l’infection sanguine, de 9,1% et 86,4%, respectivement.Conclusions: Streptococcus pneumoniae est une cause majeure d’infection sanguine dans les admissions pédiatriques en Tanzanie et est étroitement associéà l’infection à VIH. La malaria était sur-diagnostiquée cliniquement, alors que les infections bactériennes invasives étaient sous-estimées. Le VIH et les coinfections VIH contribuent à une proportion importante des admissions fébriles en pédiatrie, ce qui souligne la valeur d’un dépistage en routine du VIH.Objetivos:  Describir la contribución del VIH pediátrico y las co-infecciones con VIH en los pacientes admitidos en un hospital de Moshi, Tanzania, utilizando métodos de laboratorio contemporáneos.Métodos:  Durante un año se incluyeron de forma consecutiva todos los pacientes con edades entre los ≥2 meses y <13 años, admitidos en el hospital con fiebre o con un episodio reciente de fiebre. A todos los pacientes se les hizo una historia clínica estándar, un examen físico y pruebas de anticuerpos de VIH; también se realizaron hemocultivos aeróbicos estándar y una lámina para malaria y se anotaron los resultados al finalizar la hospitalización. Se realizó un diagnóstico temprano del VIH mediante un PCR del ARN de VIH-1 en aquellos pacientes con <18 meses. A los pacientes infectados con VIH también se les realizó una prueba de antígeno criptocócico en suero y se les determinó el porcentaje de linfocitos T CD4-positivos (CD4%).Resultados:  Se incluyeron 467 pacientes con una mediana de edad de 2 años (rango 2 meses-13 años). Un 57.2% eran niñas, y un 12.2% estaban infectadas con VIH. El diagnóstico clínico provisional de la enfermedad por VIH se realizó en un 10.7% y el de malaria en 60.4%. De los hemocultivos, en 5.8% crecieron patógenos; de estos un 25.9% eran Salmonella enterica (incluyendo 6 Salmonella typhi), y 22.2%Streptococcus pneumoniae. Se identificóPlasmodium falciparum en las láminas de 1.3% de los niños. La infección por VIH estaba asociada con infección en sangre (IS) por S. pneumoniae (odds ratio 25.7, 95% IC 2.8, 234.0), pero no había evidencia de una asociación con Escherichia coli o P. falciparum; la IS por Salmonella typhi ocurrió solo entre participantes sin infección por VIH. La sensibilidad y especificidad de un diagnóstico clínico provisional de malaria era del 100% y 40.3%; y por un diagnóstico durante la admisión de infección en sangre eran de 9.1% y 86.4%, respectivamente.Conclusiones: Streptococcus pneumoniae es una causa mayor de infección en sangre entre pacientes pediátricos admitidos en Tanzania y está muy asociado con la infección por VIH. La malaria estaba sobrediagnosticada clínicamente, mientras que la enfermedad bacteriana invasiva estaba subestimada. El VIH y las co-infecciones por VIH contribuyen a una proporción sustancial de admisiones pediátricas febriles, subestimando el valor de la prueba rutinaria para VIH.
  Tropical Medicine & International Health 04/2011; 16(7):830 - 837. · 2.80 Impact Factor
• Article: Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected children and infants in northern Tanzania.

  John A Crump, Habib O Ramadhani, Anne B Morrissey, Levina J Msuya, Lan-Yan Yang, Shein-Chung Chow, Susan C Morpeth, Hugh Reyburn, Boniface N Njau, Andrea V Shaw, Helmut C Diefenthal, John A Bartlett, John F Shao, Werner Schimana, Coleen K Cunningham, Grace D Kinabo
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  ABSTRACT: To describe the contribution of paediatric HIV and of HIV co-infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods. During 1 year, we enrolled consecutively admitted patients aged ≥2 months and <13 years with current or recent fever. All patients underwent standardized clinical history taking, a physical examination and HIV antibody testing; standard aerobic blood cultures and malaria film were also done, and hospital outcome was recorded. Early infant HIV diagnosis by HIV-1 RNA PCR was performed on those aged <18 months. HIV-infected patients also received serum cryptococcal antigen testing and had their CD4-positive T-lymphocyte count and percent determined. A total of 467 patients were enrolled whose median age was 2 years (range 2 months-13 years); Of those patients, 57.2% were female and 12.2% were HIV-infected. Admission clinical diagnosis of HIV disease was made in 10.7% and of malaria in 60.4%. Of blood cultures, 5.8% grew pathogens; of these 25.9% were Salmonella enterica (including 6 Salmonella Typhi) and 22.2%Streptococcus pneumoniae. Plasmodium falciparum was identified on blood film of 1.3%. HIV infection was associated with S. pneumoniae (odds ratio 25.7, 95% CI 2.8, 234.0) bloodstream infection (BSI), but there was no evidence of an association with Escherichia coli or P. falciparum; Salmonella Typhi BSI occurred only among HIV-uninfected participants. The sensitivity and specificity of an admission clinical diagnosis of malaria were 100% and 40.3%; and for an admission diagnosis of bloodstream infection, they were 9.1% and 86.4%, respectively. Streptococcus pneumoniae is a leading cause of bloodstream infection among paediatric admissions in Tanzania and is closely associated with HIV infection. Malaria was over-diagnosed clinically, whereas invasive bacterial disease was underestimated. HIV and HIV co-infections contribute to a substantial proportion of paediatric febrile admissions, underscoring the value of routine HIV testing.
  Tropical Medicine & International Health 04/2011; 16(7):830-7. · 2.80 Impact Factor
• Article: An Infection Control Program for a 2009 influenza A H1N1 outbreak in a university-based summer camp.

  Ephraim L Tsalik, Coleen K Cunningham, Hannah M Cunningham, Maria G Lopez-Marti, Devdutta G Sangvai, William K Purdy, Deverick J Anderson, Jessica R Thompson, Monte Brown, Christopher W Woods, L Brett Jaggers, Edward F Hendershot
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  ABSTRACT: Describe two 2009-H1N1 influenza outbreaks in university-based summer camps and the implementation of an infection control program. 7,906 campers across 73 residential camps from May 21-August 2, 2009. Influenza-like-illness (ILI) was defined as fever with cough and/or sore throat. Influenza A was identified using PCR or rapid-antigen testing. We implemented an infection control program consisting of education, hand hygiene, disinfection, symptom screening, and ILI case management. An initial ILI cluster involved 60 cases across 3 camps from June 17-July 2. Academic Camp-1 had the most cases (n = 45, 14.9% attack rate); influenza A was identified in 84% of those tested. Despite implementation of an infection control program, a second ILI cluster began on July 12 in Academic Camp-2 (n = 47, 15.0% attack rate). ILI can spread rapidly in a university-based residential camp. Infection control is an important aspect of the medical response but is challenging to implement.
  Journal of American College Health 04/2011; 59(5):419-26. · 1.45 Impact Factor
• Article: Hepatitis B vaccination in HIV-infected youth: a randomized trial of three regimens.

  Patricia M Flynn, Coleen K Cunningham, Bret Rudy, Craig M Wilson, Bill Kapogiannis, Carol Worrell, James Bethel, Dina Monte, Kelly Bojan
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  ABSTRACT: HIV-infected youth are at risk of hepatitis B infection and should be vaccinated. Previous reports suggest reduced response to standard hepatitis B vaccine regimens. HIV-infected youth, aged 12 to younger than 25 years, were randomly assigned to one of three treatment arms: Arm 1: Engerix B, 20 μg HBsAg; Arm 2: Engerix B (GlaxoSmithKline, Rixensart, Belgium), 40 μg; and Arm 3: Twinrix (GlaxoSmithKline, Rixensart, Belgium), 20 μg HBsAg combined with 720 ELU hepatitis A antigen. Vaccines were administered at Weeks 0, 4, and 24. Characteristics of evaluable patients (n = 336) at entry were similar in the study arms. At enrollment, median CD4+ T-cell count was 460 cells/mm3 (interquartile range, 305-668); 13% were less than 200 cells/mm3. Among Engerix B, 20-μg recipients, 60.4% responded to vaccine (HBsAb 10 IU/mL or greater at Week 28). Improved vaccine response was seen in recipients of Engerix B, 40 μg (73.2% versus Arm 1, P = 0.04) and Twinrix (75.4% versus Arm 1, P = 0.02). In multivariate analysis, only baseline CD4+ T-cell count and study arm were independent predictors of vaccine response. In HIV-infected youth, a three-dose vaccination regimen with Engerix B, 40 μg, or Twinrix and higher baseline CD4+ T-cell counts were independently associated with improved vaccine response.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2011; 56(4):325-32. · 4.43 Impact Factor
• Article: Birth defects among a cohort of infants born to HIV-infected women on antiretroviral medication.

  D Heather Watts, Sharon Huang, Mary Culnane, Kathleen A Kaiser, Angela Scheuerle, Lynne Mofenson, Kenneth Stanley, Marie-Louise Newell, Laurent Mandelbrot, Jean-Francois Delfraissy, Coleen K Cunningham
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  ABSTRACT: To determine rate of and risk factors for birth defects in infants born to HIV-infected women receiving nucleoside and protease inhibitor antiretroviral (ARV) therapy. Birth defects were evaluated among infants on the Pediatric AIDS Clinical Trials Group 316 trial that studied addition of peripartum nevirapine to established ARV regimen for prevention of mother-to-child transmission. Maternal therapy was categorized by trimester of earliest exposure. Birth defects were coded using conventions of the Antiretroviral Pregnancy Registry. Birth defects were detected in 60/1414 (4.2%; 95% CI 3.3-5.4%) infants including 30/636 (4.7%; 95% CI 3.2-6.7%) with first trimester ARV exposure and 30/778 (3.9%; 95% CI 2.6-5.5%) with exposure only after the first trimester (P=0.51). Rates of classes of defects were similar between first trimester compared to later exposure groups except heart defects which occurred in 16 (2.5%; 95% CI 1.4-4.1%) with first trimester ARV exposure and in six (0.8%; 95% CI 0.3-1.7%) infants with later exposure (P=0.02). Exposure to ARV was not associated with specific types of heart defects. Two cases of cardiomyopathy were noted. ARV use in early pregnancy was not associated with an increased risk of birth defects overall. The possible association of ARV exposure with heart defects requires further surveillance.
  Journal of Perinatal Medicine 12/2010; 39(2):163-70. · 1.70 Impact Factor
• Article: Establishment of haematological and immunological reference values for healthy Tanzanian children in Kilimanjaro Region

  Ann M. Buchanan, Florida J. Muro, Jean Gratz, John A. Crump, Augustine M. Musyoka, Moses W. Sichangi, Anne B. Morrissey, Jane K. M’rimberia, Boniface N. Njau, Levina J. Msuya, John A. Bartlett, Coleen K. Cunningham
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  ABSTRACT: Objective To determine the normal haematological and immunological reference intervals for healthy Tanzanian children.Methods We analysed data from 655 HIV-seronegative, healthy children from 1 month to 18 years of age from the Kilimanjaro Region of Tanzania for this cross-sectional study. Median and 95% reference ranges were determined for haematological and immunological parameters and analysed by age cohorts, and by gender for adolescents.Results Median haemoglobin (Hb) and haematocrit (Hct) for all age groups were higher than established East African reference intervals. Compared to U.S. intervals, reference ranges encompassed lower values for Hb, Hct, mean corpuscular volume, and platelets. Applying the U.S. National Institute of Health Division of AIDS (DAIDS) adverse event grading criteria commonly used in clinical trials to the reference range participants, 128 (21%) of 619 children would be classified as having an adverse event related to Hb level. CD4-positive T-lymphocyte absolute counts declined significantly with increasing age (P < 0.0001). For those aged under five years, CD4-positive T-lymphocyte percentages are lower than established developed country medians.Conclusions Country-specific reference ranges are needed for defining normal laboratory parameters among children in Africa. Knowledge of appropriate reference intervals is critical not only for providing optimal clinical care, but also for enrolling children in medical research. Knowledge of normal CD4-positive T-lymphocyte parameters in this population is especially important for guiding the practice of HIV medicine in Tanzania.Etablissement des valeurs hématologiques et immunologiques de référence chez les enfants tanzaniens sains dans la région du KilimandjaroObjectif: Déterminer les intervalles hématologiques et immunologiques de référence chez les enfants tanzaniens sains.Méthodes: Nous avons analysé les données de 655 enfants VIH séronégatifs, sains de 1 mois à 18 ans de la région de Kilimandjaro, en Tanzanie pour cette étude transversale. Les intervalles de référence médians et à 95% ont été déterminés pour les paramètres hématologiques et immunologiques, et analysés par cohortes d’âge.Résultats: Les taux d’hémoglobine médians (Hb) et d’hématocrite (Ht) pour tous les groupes d’âge étaient plus élevés que les intervalles de référence établis pour l’Afrique de l’Est. Comparés aux intervalles des États-Unis, ces valeurs de référence comprennent des valeurs inférieures pour l’Hb, l’Hct, le volume globulaire moyen et les plaquettes. En appliquant les critères de classification des événements indésirables selon la Division du SIDA de l’US National Institute of Health (DAIDS), couramment utilisés dans les essais cliniques aux intervalles de référence des participants, 128 (21%) sur 619 enfants seraient classés comme ayant un évènement indésirable associé au taux de Hb. Les taux absolus de lymphocytes T CD4-positifs diminuaient de façon significative avec l’augmentation de l’âge (P <0,0001). Pour les moins de cinq ans, les pourcentages de lymphocytes T CD4-positifs étaient inférieurs aux médianes établies pour les pays développés.Conclusions: Des intervalles de référence spécifiques aux pays sont nécessaires pour définir les paramètres de laboratoire normaux chez les enfants en Afrique. La connaissance des intervalles de référence est un élément critique non seulement pour procurer des soins cliniques optimaux, mais aussi pour le recrutement des enfants dans la recherche médicale. La connaissance des paramètres de référence des lymphocytes T CD4-positifs dans cette population est particulièrement importante pour guider dans la pratique de la médecine du VIH en Tanzanie.Establecimiento de valores de referencia hematológicos e inmunológicos para niños tanzanos sanos en la región del KilimanjaroObjetivo: Determinar los intervalos de referencia normales, tanto hematológicos como inmunológicos, para niños sanos en Tanzania.Métodos: En un estudio croseccional hemos analizado datos de 655 niños sanos, seronegativos para VIH, con edades comprendidas entre 1 mes y 18 años de la Región del Kilimanjaro en Tanzania. Se determinaron los rangos de referencia medios y del 95% para parámetros hematológicos e inmunológicos, y se realizó un análisis de cohortes por edad.Resultados: La media de la hemoglobina (Hb) y el hematocrito (Hct) en todos los grupos de edad era más alta de lo establecido en los intervalos de referencia para África del Este. Comparándolos con los intervalos para EEUU, los rangos de referencia tenían valores menores para Hb, Hct, volúmen corpuscular medio y plaquetas. Aplicando los criterios para puntuar los eventos adversos del Instituto Nacional de Estados Unidos de la División Sanitaria de SIDA utilizados comunmente para puntuar los participantes de ensayos clínicos, 128 (21%) de los 619 niños estarían clasificados como teniedo un evento adverso relacionado con el nivel Hb. Los conteos absolutos de linfocitos T CD4-positivo disminuyeron significativamente con la edad (P <0.0001). Para los menores de cinco años, los porcentajes de linfocitos T CD4-positivos eran menores que la media establecida para los países en vías de desarrollo.Conclusiones: Los rangos de referencia específicos por país son necesarios para definir los parámetros de laboratorio normales entre niños Africanos. El conocimiento de los intervalos de referencia apropiados es crítico, no solo para proveer un cuidado clínico óptimo, sino a la hora de incluír niños en estudios de investigación clínica. El conocimiento de los parámetros normales de linfocitos T CD4-positivos en esta población es especialmente importante para guiar la práctica de la medicina del VIH en Tanzania.
  Tropical Medicine & International Health 08/2010; 15(9):1011 - 1021. · 2.80 Impact Factor
• Article: Birth defects among children born to human immunodeficiency virus-infected women: pediatric AIDS clinical trials protocols 219 and 219C.

  Susan B Brogly, Mark J Abzug, D Heather Watts, Coleen K Cunningham, Paige L Williams, James Oleske, Daniel Conway, Rhoda S Sperling, Hans Spiegel, Russell B Van Dyke
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  ABSTRACT: Some studies have detected associations between in utero antiretroviral therapy (ARV) exposure and birth defects but evidence is inconclusive. A total of 2202 human immunodeficiency virus (HIV)-exposed children enrolled in the Pediatric AIDS Clinical Trials Group 219 and 219 C protocols before 1 year of age were included. Birth defects were classified using the Metropolitan Atlanta Congenital Defects Program coding. Logistic regression models were used to evaluate associations between first trimester in utero ARV exposure and birth defects. A total of 117 live-born children had birth defects for a prevalence of 5.3% (95% confidence interval [CI]: 4.4, 6.3). Prevalence did not differ by HIV infection status or overall ARV exposure; rates were 4.8% (95% CI: 3.7, 6.1) and 5.8% (95% CI: 4.2, 7.8) in children without and with first trimester ARV exposure, respectively. The defect rate was higher among children with first trimester efavirenz exposure (5/32, 15.6%) versus children without first trimester efavirenz exposure (adjusted odds ratio [aOR] = 4.31 [95% CI: 1.56, 11.86]). Protective effects of first trimester zidovudine exposure on musculoskeletal defects were detected (aOR = 0.24 [95% CI: 0.08, 0.69]), while a higher risk of heart defects was found (aOR = 2.04 [95% CI: 1.03, 4.05]). The prevalence of birth defects was higher in this cohort of HIV-exposed children than in other pediatric cohorts. There was no association with overall ARV exposure, but there were some associations with specific agents, including efavirenz. Additional studies are needed to rule out confounding and to evaluate newer ARV agents.
  The Pediatric Infectious Disease Journal 08/2010; 29(8):721-7. · 3.58 Impact Factor
• Article: Establishment of haematological and immunological reference values for healthy Tanzanian children in Kilimanjaro Region.

  Ann M Buchanan, Florida J Muro, Jean Gratz, John A Crump, Augustine M Musyoka, Moses W Sichangi, Anne B Morrissey, Jane K M'rimberia, Boniface N Njau, Levina J Msuya, John A Bartlett, Coleen K Cunningham
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  ABSTRACT: To determine the normal haematological and immunological reference intervals for healthy Tanzanian children. We analysed data from 655 HIV-seronegative, healthy children from 1 month to 18 years of age from the Kilimanjaro Region of Tanzania for this cross-sectional study. Median and 95% reference ranges were determined for haematological and immunological parameters and analysed by age cohorts, and by gender for adolescents. Median haemoglobin (Hb) and haematocrit (Hct) for all age groups were higher than established East African reference intervals. Compared to U.S. intervals, reference ranges encompassed lower values for Hb, Hct, mean corpuscular volume, and platelets. Applying the U.S. National Institute of Health Division of AIDS (DAIDS) adverse event grading criteria commonly used in clinical trials to the reference range participants, 128 (21%) of 619 children would be classified as having an adverse event related to Hb level. CD4-positive T-lymphocyte absolute counts declined significantly with increasing age (P < 0.0001). For those aged under five years, CD4-positive T-lymphocyte percentages are lower than established developed country medians. Country-specific reference ranges are needed for defining normal laboratory parameters among children in Africa. Knowledge of appropriate reference intervals is critical not only for providing optimal clinical care, but also for enrolling children in medical research. Knowledge of normal CD4-positive T-lymphocyte parameters in this population is especially important for guiding the practice of HIV medicine in Tanzania.
  Tropical Medicine & International Health 07/2010; 15(9):1011-21. · 2.80 Impact Factor
• Article: Impaired generation of hepatitis B virus-specific memory B cells in HIV infected individuals following vaccination.

  Nishaki Mehta, Coleen K Cunningham, Patricia Flynn, Joyce Pepe, Stephen Obaro, Bill G Kapogiannis, James Bethel, Katherine Luzuriaga
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  ABSTRACT: Hepatitis B-specific memory B cell (HSMBC) frequencies were measured following hepatitis B vaccination in 15 HIV uninfected and 12 HIV infected adolescents. HSMBC were detected at significantly lower frequencies in HIV infected than in HIV uninfected individuals. The detection of HBsAb >10mIU/ml at study week 28 was strongly associated with the detection of HSMBC and a direct correlation between HBsAb titers and HSMBC frequencies was observed. In HIV uninfected individuals, antibody titers >1000mIU/ml were associated with higher HSMC frequencies. Lower HSMBC frequencies, reduced memory B cell (MBC) proliferation, and altered B cell phenotypes were measured in viremic HIV infected individuals compared with aviremic HIV infected or HIV uninfected individuals.
  Vaccine 03/2010; 28(21):3672-8. · 3.77 Impact Factor
• Article: Predicting virologic failure among HIV-1-infected children receiving antiretroviral therapy in Tanzania: a cross-sectional study.

  Susan D Emmett, Coleen K Cunningham, Blandina T Mmbaga, Grace D Kinabo, Werner Schimana, Mark E Swai, John A Bartlett, John A Crump, Elizabeth A Reddy
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  ABSTRACT: Many HIV care and treatment programs in resource-limited settings rely on clinical and immunologic monitoring of antiretroviral therapy (ART), but accuracy of this strategy to detect virologic failure (VF) among children has not been evaluated. A cross-sectional sample of HIV-infected children aged 1-16 years on ART >or=6 months receiving care at a Tanzanian referral center underwent clinical staging, CD4 lymphocyte measurement, plasma HIV-1 RNA level, and complete blood count. Associations with VF (HIV-1 RNA >or=400 copies/mL) were determined utilizing bivariable and multivariate analyses; accuracy of current clinical and immunologic guidelines in identifying children with VF was assessed. Of 206 children (median age 8.7 years, ART duration 2.4 years), 65 (31.6%) demonstrated VF at enrollment. Clinical and immunological criteria identified 2 (3.5%) of 57 children with VF on first-line therapy, exhibiting 3.5% sensitivity and 100% specificity. VF was associated with younger age, receipt of nevirapine vs. efavirenz-based regimen, CD4% < 25%, and physician documentation of maladherence (P < 0.05 on bivariable analysis); the latter 2 factors remained significant on multivariate logistic regression. This study demonstrates poor performance of clinical and immunologic criteria in identifying children with virologic failure. Affordable techniques for measuring HIV-1 RNA level applicable in resource-limited settings are urgently needed.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2010; 54(4):368-75. · 4.43 Impact Factor
• Article: Clinical presentation and response to treatment of novel influenza A H1N1 in a university-based summer camp population.

  Ephraim L Tsalik, Edward F Hendershot, Devdutta G Sangvai, Hannah M Cunningham, Coleen K Cunningham, Maria G Lopez-Marti, William K Purdy, Christopher W Woods, L Brett Caram
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  ABSTRACT: Little is known about the clinical presentation and course of novel H1N1 influenza in summer camps. To describe the clinical course and evaluate the effect of influenza treatment in a summer camp population. Two large influenza outbreaks occurred in university-based residential camps between May 21 and August 2, 2009. Through active daily surveillance, medical evaluation at symptom onset, and data collection during isolation, we describe the clinical course of a large outbreak of novel H1N1 influenza. Influenza-like illness (ILI) was documented in 119 individuals. Influenza A was confirmed in 66 (79%) of 84 samples tested. Three early samples were identified as novel H1N1. ILI cases had an average age of 15.7 years and 52% were male. Sixty-three were treated with oseltamivir or zanamivir, which was initiated within 24h of diagnosis. Cough, myalgia and sore throat occurred in 69, 64 and 63% of cases, respectively. The highest temperature over the course of illness (T(max)) occurred within 48h after symptom onset in 87.5% of individuals. Average T(max) was 38.4 degrees C (range 36.1-40.2 degrees C). Among confirmed influenza cases, 69% defervesced by 72h and 95% defervesced by 96h. Defervescence at 72h was not different in the treated and untreated groups (p=0.12). Novel H1N1 generally has a mild, self-limited course in healthy adolescent campers. Defervescence occurred within 72h and was unaffected by treatment.
  Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 03/2010; 47(3):286-8. · 3.12 Impact Factor
• Article: Randomized trial to determine safety and immunogenicity of two strategies for hepatitis B vaccination in healthy urban adolescents in the United States.

  Coleen K Cunningham, Bret J Rudy, Jiahong Xu, James Bethel, Bill G Kapogiannis, Sushma Ahmad, Craig M Wilson, Patricia M Flynn
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  ABSTRACT: Multiple studies have shown excellent response rates after hepatitis B immunization in youth; however, one previous study conducted in urban youth demonstrated poor responses. Urban youth, ages 12 to 17 years, at participating Adolescent Medicine Trials Network for HIV/AIDS Interventions Clinical/Research sites were randomized to receive either 2 doses of Recombivax HB (10 microg hepatitis B surface antigen) or Twinrix (20 microg hepatitis B surface antigen and 720 EL.U hepatitis A antigen) at 0 and 24 weeks. Safety data were collected and antibody measures performed at 0, 28, and 76 weeks. A total of 123 subjects were enrolled and 102 had week 28 serum samples available for antibody measure. A positive response (serum antibody > or =10 mIU/mL) to hepatitis B antigen was documented in 41 of 47 (87.2%; 95% confidence interval [CI] 74.3%-95.2%) Recombivax HB recipients and in 52 of 55 (94.6%; 95% CI, 84.9%-98.9%) Twinrix recipients (P = 0.295). In an adjusted analysis, those identified as Hispanic ethnicity (N = 86) were more likely to have a positive response (odds ratio 7.38, 95% CI, 1.56-34.95; P = 0.0018); whereas those who identified as not heterosexual (N = 9) were less likely to respond (odds ratio = 0.12, 95% CI, 0.02-0.74). The majority of youth in the Twinrix arm were hepatitis A antibody positive at baseline (26/51; 51%); however, 24 of 25 hepatitis A antibody negative youth responded to the hepatitis A component. Both vaccines were safe. Response rate to 2 doses of Recombivax HB in urban youth is lower than previous studies suggest. The factors associated with diminished response are not known.
  The Pediatric Infectious Disease Journal 02/2010; 29(6):530-4. · 3.58 Impact Factor
• Article: Advances and failures in preventing perinatal human immunodeficiency virus infection.

  Ann M Buchanan, Coleen K Cunningham
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  ABSTRACT: An estimated 2.5 million children are currently living with HIV, the vast majority as a result of mother-to-child transmission. Prevention of perinatal HIV infection has been immensely successful in developed countries. A comprehensive package of services, including maternal and infant antiretroviral therapy, elective cesarean section, and avoidance of breast-feeding, has resulted in transmission rates of less than 2%. However, in developing countries, access to such services is often not available, as demonstrated by the fact that the vast majority of children with HIV live in Africa. Over the past few years, many developing nations have made great strides in improving access to much-needed services. Notably, in eastern and southern Africa, the regions most affected by HIV, mother-to-child-transmission coverage rates for HIV-positive women increased from 11% in 2004 to 31% in 2006. These successes are deserving of recognition, while not losing sight of the fact that much remains to be done; currently, an estimated 75% of pregnant women worldwide have an unmet need for antiretroviral therapy. Further work is needed to determine the optimal strategy for reducing perinatal transmission among women in resource-poor settings, with a particular need for reduction of transmission via breast-feeding.
  Clinical microbiology reviews 08/2009; 22(3):493-507. · 14.69 Impact Factor
• Article: Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable viral loads on durable suppressive highly active antiretroviral therapy.

  Carlum Shiu, Coleen K Cunningham, Thomas Greenough, Petronella Muresan, Victor Sanchez-Merino, Vincent Carey, J Brooks Jackson, Carrie Ziemniak, Lawrence Fox, Marvin Belzer, Stuart C Ray, Katherine Luzuriaga, Deborah Persaud
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  ABSTRACT: In most human immunodeficiency virus type 1 (HIV-1)-infected individuals who achieve viral loads of <50 copies/ml during highly active antiretroviral therapy (HAART), low levels of plasma virus remain detectable for years by ultrasensitive methods. The relative contributions of ongoing virus replication and virus production from HIV-1 reservoirs to persistent low-level viremia during HAART remain controversial. HIV-1 vaccination of HAART-treated individuals provides a model for examining low-level viremia, as immunizations may facilitate virus replication and sequence evolution. In a phase 1 trial of modified vaccinia virus Ankara/fowlpox virus-based HIV-1 vaccines in 20 HIV-infected young adults receiving HAART, we assessed the prevalence of low-level viremia and sequence evolution, using ultrasensitive viral load (<6.5 copies/ml) and genotyping (five-copy sensitivity) assays. Viral evolution, consisting of new drug resistance mutations and novel amino acid changes within a relevant HLA-restricted allele (e.g., methionine, isoleucine, glutamine, or arginine for leucine at position 205 of RT), was found in 1 and 3 of 20 subjects, respectively. Sequence evolution was significantly correlated with levels of viremia of between 6.5 and <50 copies/ml (P = 0.03) and was more likely to occur within epitopes presented by relevant HLA alleles (P < 0.001). These findings suggest that ongoing virus replication contributes to low-level viremia in patients on HAART and that this ongoing replication is subject to CD8(+) T-cell selective pressures.
  Journal of Virology 07/2009; 83(19):9731-42. · 5.40 Impact Factor
• Article: Short-cycle therapy in adolescents after continuous therapy with established viral suppression: the impact on viral load suppression.

  Bret J Rudy, John Sleasman, Bill Kapogiannis, Craig M Wilson, James Bethel, Leslie Serchuck, Sushma Ahmad, Coleen K Cunningham
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  ABSTRACT: This was a proof-of-principle study to evaluate the impact of short cycle therapy (SCT; 4 days on/3 days off) in adolescents and young adults with good viral suppression on a protease inhibitor-based antiretroviral regimen. Subjects were recruited by the Adolescent Trials Network for HIV/AIDS Interventions and the Pediatric AIDS Clinical Trials Group. Subjects were infected either through perinatal/early childhood transmission or later via risk behaviors. All subjects were required to have at least 6 months of documented viral suppression below 400 copies/ml plus a preentry value below 200 copies/ml and an entry CD4+ T cell count above 350 cells/mm3. Of the 32 subjects enrolled, 12 (37.5%) had confirmed viral load rebound >400 copies, with 18 subjects (56%) coming off for any reason. The majority of subjects resuppressed when placed back onto continuous therapy using the same agents. Although no difference was found in virologic rebound rates between the early and later transmission groups, those infected early in life had higher rates of coming off SCT for any reason. There was no impact of SCT on the CD4+ T cell counts in those who remained on study or those who came off SCT for any reason. Subjects demonstrated good adherence to the SCT regimen. This study suggests that further evaluation of SCT may be warranted in some groups of adolescents and young adults infected with HIV.
  AIDS research and human retroviruses 06/2009; 25(6):555-61. · 2.18 Impact Factor