Utility of clinical parameters to identify HIV infection in infants below ten weeks of age in South Africa: a prospective cohort study
Tóm tắt
As HIV-infected infants have high mortality, the World Health Organization now recommends initiating antiretroviral therapy as early as possible in the first year of life. However, in many settings, laboratory diagnosis of HIV in infants is not readily available. We aimed to develop a clinical algorithm for HIV presumptive diagnosis in infants < 10 weeks old using screening data from the Children with HIV Early Antiretroviral therapy (CHER) study in South Africa. HIV-infected and HIV-uninfected exposed infants < 10 weeks of age were identified through Vertical Transmission Prevention programs. Clinical and laboratory data were systematically recorded, groups were compared using Kruskal-Wallis, analysis of variance (ANOVA), and Fisher's exact tests. Receiver Operating Characteristic (ROC) curves were compiled using combinations of clinical findings. 417 HIV-infected and 125 HIV-exposed, uninfected infants, median age 46 days (IQR 38-55), were included. The median CD4 percentage in HIV-infected infants was 34 (IQR 28-41)%. HIV-infected infants had lower weight-for-age, more lymphadenopathy, oral thrush, and hepatomegaly than exposed uninfected infants (Adjusted Odds Ratio 0.51, 8.8, 5.6 and 23.5 respectively; p < 0.001 for all). Sensitivity of individual signs was low (< 20%) but specificity high (98-100%). If any one of oral thrush, hepatomegaly, splenomegaly, lymphadenopathy, diaper dermatitis, weight < 50th centile are present, sensitivity for HIV infection amongst HIV-exposed infants was 86%. These algorithms performed similarly when used to predict severe immune suppression. A combination of physical findings is helpful in identifying infants most likely to be HIV-infected. This may inform management algorithms and provide guidance for focused laboratory testing in some settings, and should be further validated in these settings and elsewhere.
Tài liệu tham khảo
Newell ML, Brahmbhatt H, Ghys PD: Child mortality and HIV infection in Africa: a review. AIDS. 2004, 18: S27-S34.
Newell ML, Coovadia H, Cortina-Borja M, Rollins N, Gaillard P, Dabis F, Ghent International AIDS Society (IAS) Working Group on HIV infection in Women and Children: Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet. 2004, 364: 1236-1243. 10.1016/S0140-6736(04)17140-7.
Brahmbhatt H, Kigozi G, Wabwire-Mangen F, Serwadda D, Nalugoda F, Sewankambo N, Lutalo T, Kidduggavu M, Wawer M, Gray R: Mortality in HIV-infected and uninfected children of HIV-infected and uninfected mothers in rural Uganda. J Acquir Immune Defic Syndr. 2006, 41: 504-508. 10.1097/01.qai.0000188122.15493.0a.
Violari A, Cotton M, Gibb D, Babiker AG, Steyn J, Madhi SA, Jean-Philippe P, McIntyre JA, The CHER Study Team: ART initiated before 12 weeks reduces early mortality in young HIV-infected infants: evidence from the Children with HIV Early Antiretroviral Therapy (CHER) Study. N Engl J Med. 2008, 358: 2233-2244.
McNally LM, Jeena PM, Gajee K, Thula S, Sturm AW, Cassol S, Tomkins AM, Coovadia AH, Goldblatt D: Effect of age, polymicrobial disease, and maternal HIV status on treatment response and cause of severe pneumonia in South African children: a prospective descriptive study. Lancet. 2007, 369: 1440-1451. 10.1016/S0140-6736(07)60670-9.
Dunn DT, HIV Paediatric Prognostic Markers Collaborative Study: Short-term risk of disease progression in HIV-1-infected children receiving no antiretroviral therapy or zidovudine monotherapy: a meta-analysis. Lancet. 2003, 362: 1605-1611.
World Health Organisation: Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access. 2006, Geneva
World Health Organisation: Report of the WHO Technical Reference Group, Paediatric HIV/ART Care Guideline Reference Group Meeting. 2008, Geneva, Switzerland
Iliff PJ, Ntozini R, Nathoo KJ, Piwoz E, Moulton L, ZVITAMBO Study: Making a working clinical diagnosis of HIV infection in infants in Zimbabwe. Trop Med Int Health. 2008, 13: 1459-1469. 10.1111/j.1365-3156.2008.02178.x.
Jones SA, Sherman GG, Coovadia AH: Can clinical algorithms deliver an accurate diagnosis of HIV infection in infancy?. Bull World Health Organ. 2005, 83: 559-560.
Chintu C, Malek A, Nyumbu M, Luo C, Masona J, DuPost HL, Zumla A: Case definitions for paediatric AIDS: the Zambian experience. Int J STD AIDS. 1993, 4: 83-85.
Lepage P, van de Perre P, Dabis F, Comenges D, Orbinski J, Hitimana DG, Bazubagira A, van Goethem C, Allen S, Butzler JP: Evaluation and simplification of the World Health Organization clinical case definition for paediatric AIDS. AIDS. 1989, 3: 221-225. 10.1097/00002030-198904000-00005.
World Health Organisation: Report on the Workshop on Adaptation of IMCI Guidelines to include HIV/AIDS. 2001, Harare, Zimbabwe, Accessed June 15 2008, [http://www.who.int/]
Rouet F, Elenga N, Msellati P, eMontcho C, Viho I, Sakaravitch C, Danel C, Rouzioux C, Leroy V, Dabis F, ANRS 049 Abidjan DITRAME Study: Primary HIV-1 infection in African children infected through breastfeeding. AIDS. 2002, 16: 2303-9. 10.1097/00002030-200211220-00010.
Richardson BA, Nduati R, Mbori-Ngacha D, Overbaugh J, John-Stewart GC: Acute HIV infection among Kenyan Infants. Clin Infect Dis. 2008, 46: 289-95. 10.1086/524748.
Sherman GG, Matsebula TC, Jones SA: Is early HIV testing of infants in poorly resourced prevention of mother to child transmission programmes unaffordable?. Trop Med Int Health. 2005, 10: 1108-1113. 10.1111/j.1365-3156.2005.01495.x.
The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/11/104/prepub