ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
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UNAIDS, 2016. The Prevention Gap Report. Geneva, Switzerland: United Nations.
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Hsiao NY, Stinson K, Myer L, 2013. Linkage of HIV-infected infants from diagnosis to antiretroviral therapy services across the Western Cape, South Africa. PLoS One 8: e55308.
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Kagaayi J, Makumbi F, Nakigozi G, Wawer MJ, Gray RH, Serwadda D, Reynolds SJ, 2007. WHO HIV clinical staging or CD4 cell counts for antiretroviral therapy eligibility assessment? An evaluation in rural Rakai district, Uganda. AIDS 21: 1208–1210.
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13.
O’Hare B, Milner DA Jr, Newberry L, Pelani I, Malisita K, 2014. Discordance between clinical and immunological ART eligibility criteria for children in Malawi. BMC Res Notes 7: 666.
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14.
WHO, 2015. Guideline on When to Start Antiretroviral Therapy and on Pre-Exposure Prophylaxis for HIV. Geneva, Switzerland: WHO.
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15.
WHO, 2016. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. Geneva, Switzerland: WHO.
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Kankasa C et al. 2009. Routine offering of HIV testing to hospitalized pediatric patients at university teaching hospital, Lusaka, Zambia: acceptability and feasibility. J Acquir Immune Defic Syndr 51: 202–208.
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17.
Chamla D et al. 2013. Evidence from the field: missed opportunities for identifying and linking HIV-infected children for early initiation of ART. AIDS 27 (Suppl 2): S139–S146.
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18.
Rogerson SR, Gladstone M, Callaghan M, Erhart L, Rogerson SJ, Borgstein E, Broadhead RL, 2004. HIV infection among paediatric in-patients in Blantyre, Malawi. Trans R Soc Trop Med Hyg 98: 544–552.
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19.
Zwi K, Pettifor J, Soderlund N, Meyers T, 2000. HIV infection and in-hospital mortality at an academic hospital in South Africa. Arch Dis Child 83: 227–230.
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20.
Grabar S, Selinger-Leneman H, Abgrall S, Pialoux G, Weiss L, Costagliola D, 2009. Prevalence and comparative characteristics of long-term nonprogressors and HIV controller patients in the French Hospital Database on HIV. AIDS 23: 1163–1169.
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21.
Pantaleo G et al. 1995. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Engl J Med 332: 209–216.
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22.
Paul ME, Mao C, Charurat M, Serchuck L, Foca M, Hayani K, Handelsman EL, Diaz C, McIntosh K, Shearer WT, 2005. Predictors of immunologic long-term nonprogression in HIV-infected children: implications for initiating therapy. J Allergy Clin Immunol 115: 848–855.
-
23.
Gulia J, Kumwenda N, Li Q, Taha TE, 2007. HIV seroreversion time in HIV-1-uninfected children born to HIV-1-infected mothers in Malawi. J Acquir Immune Defic Syndr 46: 332–337.
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24.
Gutierrez M, Ludwig DA, Khan SS, Chaparro AA, Rivera DM, Cotter AM, Scott GB, 2012. Has highly active antiretroviral therapy increased the time to seroreversion in HIV exposed but uninfected children? Clin Infect Dis 55: 1255–1261.
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25.
Klarkowski D, Glass K, O’Brien D, Lokuge K, Piriou E, Shanks L, 2013. Variation in specificity of HIV rapid diagnostic tests over place and time: an analysis of discordancy data using a Bayesian approach. PLoS One 8: e81656.
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Klarkowski DB, Wazome JM, Lokuge KM, Shanks L, Mills CF, O’Brien DP, 2009. The evaluation of a rapid in situ HIV confirmation test in a programme with a high failure rate of the WHO HIV two-test diagnostic algorithm. PLoS One 4: e4351.
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Shanks L, Siddiqui MR, Kliescikova J, Pearce N, Ariti C, Muluneh L, Pirou E, Ritmeijer K, Masiga J, Abebe A, 2015. Evaluation of HIV testing algorithms in Ethiopia: the role of the tie-breaker algorithm and weakly reacting test lines in contributing to a high rate of false positive HIV diagnoses. BMC Infect Dis 15: 39.
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Gasasira AF, Dorsey G, Kamya MR, Havlir D, Kiggundu M, Rosenthal PJ, Charlebois ED, 2006. False-positive results of enzyme immunoassays for human immunodeficiency virus in patients with uncomplicated malaria. J Clin Microbiol 44: 3021–3024.
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41.
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UNAIDS/WHO, 2013. Working Group on Global HIV/AIDS and STI Surveillance: Paediatric HIV Surveillance Among Infants and Children Less Than 18 Years of Age. Geneva, Switzerland: World Health Organization.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 219 | 156 | 7 |
| Full Text Views | 351 | 14 | 0 |
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Rapid Diagnostic Testing of Hospitalized Malawian Children Reveals Opportunities for Improved HIV Diagnosis and Treatment
Theresa F. Madaline
Theresa F. Madaline
Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York;
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Sarah E. Hochman
Sarah E. Hochman
Department of Medicine, New York University Langone Medical Center and New York University School of Medicine, New York, New York;
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Karl B. Seydel
Karl B. Seydel
Department of Osteopathic Medical Specialties, Michigan State University College of Osteopathic Medicine, East Lansing, Michigan;
Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi;
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Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi;
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Alice Liomba
Alice Liomba
Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi;
Department of Paediatrics and Child Health, University of Malawi College of Medicine, Blantyre, Malawi;
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Department of Paediatrics and Child Health, University of Malawi College of Medicine, Blantyre, Malawi;
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Alex Saidi
Alex Saidi
Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi;
Department of Paediatrics and Child Health, University of Malawi College of Medicine, Blantyre, Malawi;
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Department of Paediatrics and Child Health, University of Malawi College of Medicine, Blantyre, Malawi;
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Grace Matebule
Grace Matebule
Department of Paediatrics and Child Health, University of Malawi College of Medicine, Blantyre, Malawi;
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Wenzhu B. Mowrey
Wenzhu B. Mowrey
Department of Epidemiology & Population Health, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York;
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Bernadette O’Hare
Bernadette O’Hare
Department of Paediatrics and Child Health, University of Malawi College of Medicine, Blantyre, Malawi;
Global Health Implementation, University of St. Andrews School of Medicine, North Haugh, United Kingdom;
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Global Health Implementation, University of St. Andrews School of Medicine, North Haugh, United Kingdom;
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Danny A. Milner Jr.
Danny A. Milner Jr.
American Society for Clinical Pathology, Chicago, Illinois;
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Kami Kim
Kami Kim
Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York;
Departments of Pathology and Microbiology and Immunology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York
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Departments of Pathology and Microbiology and Immunology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York
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Recent World Health Organization (WHO) guidelines recommend antiretroviral therapy (ART) for all HIV-infected people; previously CD4+ T lymphocyte quantification (CD4 count) or clinical staging determined eligibility for children ≥ 5 years old in low- and middle-income countries. We examined positive predictive value (PPV) of a rapid diagnostic test (RDT) algorithm and ART eligibility for hospitalized children with newly diagnosed HIV infection. We enrolled 363 hospitalized Malawian children age 2 months to 16 years with two serial positive HIV RDT from 2013 to 2015. Children aged ≤ 18 months whose nucleic acid testing was negative or unavailable were later excluded from the analysis (N = 16). If RNA PCR was undetectable, human immunodeficiency virus (HIV) enzyme immunoassay (EIA) and western blot (WB) were performed. Those with negative or discordant EIA and WB were considered HIV negative and excluded from further analysis (N = 6). ART eligibility was assessed using age, CD4 count, and clinical HIV stage. Among 150 patients with HIV RNA PCR results, 15 had undetectable HIV RNA. Of those, EIA and WB were positive in nine patients and negative or discordant in six patients. PPV of serial RDT was 90% versus RNA PCR alone and 96% versus combined RNA PCR, EIA, and WB. Of all patients aged ≥ 5 years, 8.9% were ineligible for ART under previous WHO guidelines. Improved HIV testing algorithms are needed for accurate diagnosis of HIV infection in children as prevalence of pediatric HIV declines. Universal treatment will significantly increase the numbers of older children who qualify for ART.
- Supplemental Materials (PDF 919 KB)
Author Notes
Financial support: This work was supported by the Albert Einstein College of Medicine Global Health Center Microgrant Program [to TFM and KK]; the Burke Global Health Fellowship Award [to DAM]; a Pilot Award from the Montefiore-Einstein Center for AIDS Research and the National Institutes of Health [grant number P30 AI051519 to SEH]; National Institutes of Health [grant number R01 AI34969-14 to KBS]; and the UNC Malawi Project Lilongwe Laboratory and the National Institutes of Health [grant number 2UM1AI069423].
Authors’ addresses: Theresa F. Madaline, Division of Infectious Diseases, Montefiore Medical Center and Albert Einstein College of Medicine, Belfer Building, Bronx, NY, E-mail: tmadalin@montefiore.org. Sarah E. Hochman, New York University Langone Medical Center and New York University School of Medicine, Greenberg Hall, SC1, New York, NY, E-mail: sarah.hochman@nyumc.org. Karl B. Seydel, Department of Osteopathic Medical Specialties, Michigan State University College of Osteopathic Medicine, Blantyre Malaria Project, Blantyre, Malawi, E-mail: seydel@msu.edu. Alice Liomba and Alex Saidi, Blantyre Malaria Project, Blantyre, Malawi, E-mails: wanguialice@gmail.com and alexmsaidi@gmail.com. Grace Matebule, Queen Elizabeth Central Hospital, Blantyre, Malawi, Wenzhu Bi Mowrey, Division of Biostatistics, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, E-mail: wenzhu.mowrey@einstein.yu.edu. Bernadette O’Hare, Department of Paediatrics and Child Health, Queen Elizabeth Central Hospital, Blantyre, Malawi, E-mail: bernadetteaohare@gmail.com. Danny A. Milner Jr., Center for Global Health, American Society for Clinical Pathology, Chicago, IL, E-mail: dan.milner@ascp.org. Kami Kim, Albert Einstein College of Medicine, Bronx, NY, E-mail: kami.kim@einstein.yu.edu.
These authors contributed equally to this work.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
2.
UNAIDS, 2016. Children and HIV Fact Sheet. Geneva, Switzerland: United Nations.
-
3.
UNAIDS, 2016. The Prevention Gap Report. Geneva, Switzerland: United Nations.
-
4.
WHO/UNAIDS, 2014. 2014 Global Update on the Health Sector Response to HIV. Geneva, Switzerland: World Health Organization.
-
6.
UNAIDS, 2013. Global Report: UNAIDS Report on The Global AIDS Epidemic 2013. Geneva, Switzerland: United Nations.
-
7.
Hsiao NY, Stinson K, Myer L, 2013. Linkage of HIV-infected infants from diagnosis to antiretroviral therapy services across the Western Cape, South Africa. PLoS One 8: e55308.
-
8.
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12.
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-
13.
O’Hare B, Milner DA Jr, Newberry L, Pelani I, Malisita K, 2014. Discordance between clinical and immunological ART eligibility criteria for children in Malawi. BMC Res Notes 7: 666.
-
14.
WHO, 2015. Guideline on When to Start Antiretroviral Therapy and on Pre-Exposure Prophylaxis for HIV. Geneva, Switzerland: WHO.
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15.
WHO, 2016. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. Geneva, Switzerland: WHO.
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Kankasa C et al. 2009. Routine offering of HIV testing to hospitalized pediatric patients at university teaching hospital, Lusaka, Zambia: acceptability and feasibility. J Acquir Immune Defic Syndr 51: 202–208.
-
17.
Chamla D et al. 2013. Evidence from the field: missed opportunities for identifying and linking HIV-infected children for early initiation of ART. AIDS 27 (Suppl 2): S139–S146.
-
18.
Rogerson SR, Gladstone M, Callaghan M, Erhart L, Rogerson SJ, Borgstein E, Broadhead RL, 2004. HIV infection among paediatric in-patients in Blantyre, Malawi. Trans R Soc Trop Med Hyg 98: 544–552.
-
19.
Zwi K, Pettifor J, Soderlund N, Meyers T, 2000. HIV infection and in-hospital mortality at an academic hospital in South Africa. Arch Dis Child 83: 227–230.
-
20.
Grabar S, Selinger-Leneman H, Abgrall S, Pialoux G, Weiss L, Costagliola D, 2009. Prevalence and comparative characteristics of long-term nonprogressors and HIV controller patients in the French Hospital Database on HIV. AIDS 23: 1163–1169.
-
21.
Pantaleo G et al. 1995. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Engl J Med 332: 209–216.
-
22.
Paul ME, Mao C, Charurat M, Serchuck L, Foca M, Hayani K, Handelsman EL, Diaz C, McIntosh K, Shearer WT, 2005. Predictors of immunologic long-term nonprogression in HIV-infected children: implications for initiating therapy. J Allergy Clin Immunol 115: 848–855.
-
23.
Gulia J, Kumwenda N, Li Q, Taha TE, 2007. HIV seroreversion time in HIV-1-uninfected children born to HIV-1-infected mothers in Malawi. J Acquir Immune Defic Syndr 46: 332–337.
-
24.
Gutierrez M, Ludwig DA, Khan SS, Chaparro AA, Rivera DM, Cotter AM, Scott GB, 2012. Has highly active antiretroviral therapy increased the time to seroreversion in HIV exposed but uninfected children? Clin Infect Dis 55: 1255–1261.
-
25.
Klarkowski D, Glass K, O’Brien D, Lokuge K, Piriou E, Shanks L, 2013. Variation in specificity of HIV rapid diagnostic tests over place and time: an analysis of discordancy data using a Bayesian approach. PLoS One 8: e81656.
-
26.
Klarkowski DB, Wazome JM, Lokuge KM, Shanks L, Mills CF, O’Brien DP, 2009. The evaluation of a rapid in situ HIV confirmation test in a programme with a high failure rate of the WHO HIV two-test diagnostic algorithm. PLoS One 4: e4351.
-
27.
Shanks L, Siddiqui MR, Kliescikova J, Pearce N, Ariti C, Muluneh L, Pirou E, Ritmeijer K, Masiga J, Abebe A, 2015. Evaluation of HIV testing algorithms in Ethiopia: the role of the tie-breaker algorithm and weakly reacting test lines in contributing to a high rate of false positive HIV diagnoses. BMC Infect Dis 15: 39.
-
28.
Gray RH, Makumbi F, Serwadda D, Lutalo T, Nalugoda F, Opendi P, Kigozi G, Reynolds SJ, Sewankambo NK, Wawer MJ, 2007. Limitations of rapid HIV-1 tests during screening for trials in Uganda: diagnostic test accuracy study. BMJ 335: 188.
-
29.
Kroidl I, Clowes P, Mwalongo W, Maganga L, Maboko L, Kroidl AL, Geldmacher C, Machibya H, Hoelscher M, Saathoff E, 2012. Low specificity of determine HIV1/2 RDT using whole blood in south west Tanzania. PLoS One 7: e39529.
-
30.
Klarkowski D, O’Brien DP, Shanks L, Singh KP, 2014. Causes of false-positive HIV rapid diagnostic test results. Expert Rev Anti Infect Ther 12: 49–62.
-
31.
Gasasira AF, Dorsey G, Kamya MR, Havlir D, Kiggundu M, Rosenthal PJ, Charlebois ED, 2006. False-positive results of enzyme immunoassays for human immunodeficiency virus in patients with uncomplicated malaria. J Clin Microbiol 44: 3021–3024.
-
32.
WHO, 2015. HIV Assays: Laboratory Performance and Other Operational Characteristics: Rapid Diagnostic Tests (Combined Detection of HIV-1/2 Antibodies and Discriminatory Detection of HIV-1 and HIV-2 Antibodies): Report 18. Geneva, Switzerland: WHO.
-
33.
Tu XM, Litvak E, Pagano M, 1992. Issues in human immunodeficiency virus (HIV) screening programs. Am J Epidemiol 136: 244–255.
-
34.
Shanks L, Klarkowski D, O’Brien DP, 2013. False positive HIV diagnoses in resource limited settings: operational lessons learned for HIV programmes. PLoS One 8: e59906.
-
35.
Penazzato M, Crowley S, Mofenson L, Franceschetto G, Nannyonga MM, Mazza A, Giaquinto C, 2012. Programmatic impact of the evolution of WHO pediatric antiretroviral treatment guidelines for resource-limited countries (Tukula Fenna Project, Uganda). J Acquir Immune Defic Syndr 61: 522–525.
-
36.
Lisse I, Samb B, Whittle H, Jensen H, Soumare M, Simondon F, Aaby P, 1998. Acute and long-term changes in T-lymphocyte subsets in response to clinical and subclinical measles. A community study from rural Senegal. Scand J Infect Dis 30: 17–21.
-
37.
Lisse IM, Aaby P, Whittle H, Knudsen K, 1994. A community study of T lymphocyte subsets and malaria parasitaemia. Trans R Soc Trop Med Hyg 88: 709–710.
-
38.
WHO, 2013. Data Repository Causes of Child Mortality. Geneva, Switzerland: World Health Organization. Available at: http://www.who.int/gho/child_health/mortality/causes/en/. Accessed March 25, 2015.
-
39.
Glynn JR, Murray J, Bester A, Nelson G, Shearer S, Sonnenberg P, 2008. Effects of duration of HIV infection and secondary tuberculosis transmission on tuberculosis incidence in the South African gold mines. AIDS 22: 1859–1867.
-
40.
Hochman SE et al. 2015. Fatal pediatric cerebral malaria is associated with intravascular monocytes and platelets that are increased with HIV coinfection. MBio 6: e01390–e01415. Erratum in: MBio 2016;7(1).
-
41.
Bronzan RN et al. 2007. Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome. J Infect Dis 195: 895–904.
-
42.
Kranzer K, Meghji J, Bandason T, Dauya E, Mungofa S, Busza J, Hatzold K, Kidia K, Mujuru H, Ferrand RA, 2014. Barriers to provider-initiated testing and counselling for children in a high HIV prevalence setting: a mixed methods study. PLoS Med 11: e1001649.
-
43.
UNAIDS/WHO, 2013. Working Group on Global HIV/AIDS and STI Surveillance: Paediatric HIV Surveillance Among Infants and Children Less Than 18 Years of Age. Geneva, Switzerland: World Health Organization.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 219 | 156 | 7 |
| Full Text Views | 351 | 14 | 0 |
| PDF Downloads | 109 | 7 | 0 |