204 results on '"Kankasa C"'
Search Results
2. P02-07. High concentrations of interleukin-15 and low concentrations of CCL5 in breast milk are associated with protection against postnatal HIV transmission
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Thea DM, Kankasa C, Sinkala M, Semrau K, Kuhn L, Ghosh MK, Walter J, and Aldrovandi GM
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2009
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3. Déterminants du faible poids de naissance chez des enfants nés de mères séropositives pour le VIH, non éligibles au traitement antirétroviral, en Afrique
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Traore, H., Meda, N., Nagot, N., Somé, E., Neboua, D., Kankasa, C., Hofmeyr, J., Tumwine, J., Vallo, R., Ye, D., Tylleskar, T., and Van de Perre, P.
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- 2013
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4. Errata: Distribution of Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus Type 8 in Zambian Maternal Saliva and Breastmilk: Implifications for Transmission
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Brayfield, B. P., Kankasa, C., and West, J. T.
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- 2004
5. Strategies for nevirapine initiation in HIV-infected children taking pediatric fixed-dose combination 'Baby Pills' in Zambia: a randomized controlled trial
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Mulenga, V., Cook, A., Walker, A.S., Kabamba, D., Chijoka, C., Ferrier, A., Kalengo, C., Kityo, C., Kankasa, C., Burger, D., Thomason, M., Chintu, C., and Gibb, D.M.
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Nevirapine -- Usage ,Nevirapine -- Health aspects ,HIV infection -- Drug therapy ,HIV infection -- Patient outcomes ,Drug therapy -- Usage ,Drug therapy -- Patient outcomes ,Children -- Diseases ,Children -- Drug therapy ,Health ,Health care industry - Published
- 2010
6. HLA-G 14 bp deletion/insertion polymorphism and mother-to-child transmission of HIV
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Segat, L., Zupin, L., Kim, H.-Y., Catamo, E., Thea, D. M., Kankasa, C., Aldrovandi, G. M., Kuhn, L., and Crovella, S.
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- 2014
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7. Factors associated with HIV prevalence in a pre-partum cohort of Zambian women
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St Lawrence, J S, Klaskala, W, Kankasa, C, West, J T, Mitchell, C D, and Wood, C
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- 2006
8. Epidemiological Characteristics of Human Herpesvirus-8 Infection in a Large Population of Antenatal Women in Zambia
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Klaskala, W., Brayfield, B. P., Kankasa, C., Bhat, G., West, J. T., Mitchell, C. D., and Wood, Charles
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- 2005
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9. Prevalence of clinical, immunological and irological failure among children on Haart at the university teaching hospital, Lusaka, Zambia
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Ginwalla, R, Chama, E, Kawamya-Banda, F, Thomas, R, Mwiya, M, and Kankasa, C
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Background: There is increasing evidence that the current clinical and immunological monitoring tools are not sufficient to identify early enough patients who are failing on treatment. Development of resistance to the limited treatment options for children and premature switching are the dangers. The objective of this study was to review patient records to see how well WHO staging, CD4 profiles and viral load estimations relate in children on treatment at the University Teaching Hospital (UTH).Methods: A retrospective chart review of all children aged between 0-19 years that started treatment between January 2004 and Dec 2010 was carried out at the UTH. Systematic sampling was done of every second child who received HAART for more than 24 weeks, with at least one viral load (VL) reading beyond 24 weeks of treatment. Six-monthly clinical (WHO staging) immunological (age- related CD4 count/%) and virological data were collected until last follow-up review or five years on treatment. The 2010 Zambian Pediatric Guidelines were used to gauge age-related clinical, immunological and virological failure (VL> 1,000).Results: A total of 517 patient records were reviewed (table 1). Mean age at ART initiation was 7 years ((SD 4.7yrs). Mean time after ART initiation when first viral load test was done was 2.7 years (SD 1.5yrs). Of all the viral loads done, 64% (328) had a routine indication for patients on treatment nearing the 3 year mark (mean 2.7 years). In 40% of children the first viral load test result was above 1,000 after 24 weeks or more of treatment. A total of 482 patients had WHO staging done at the time first VL test was done. Of the 359 patients (table 2) with a clinical stage I/II (not severely immunosuppressed), 41% were failing virologically. On the other hand, 63% of the patients with clinical stage III/IV had a VL below 1,000. Table 3 shows that there were 509 patients who had an immunological staging done at the time first VL was done. Of the 106 patients who were failing immunologically, 28% were virologically well suppressed. On the other hand of the 403 who were immunologically doing fine, 32% were failing virologically.Conclusions: Clinical staging and Immunological monitoring in children on ART does not accurately identify those that are failing. A push for routine, affordable virological testing is needed to identify treatment failures early to prevent development of ART resistance and to avoid premature switches to second line in those who are actually well suppressed.
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- 2014
10. Infant peri-exposure prophylaxis for 12 months to eliminate breastfeeding transmission of HIV-1 in Africa. The ANRS 12174 cohort
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Tylleskär, T, Nagot, N, Kankasa, C, Meda, N, Tumwine, J, Hofmeyr, J, Mwiya, M, Siuluta, C, Traore, H, Kwagala, M, Sunday, A, Singata, M, Vallo, R, Maréchal, V, Some, E, Rutagwera, D, Neboua, D, Ndeezi, G, Neveu, D, Jackson, D, Lombard, C, Blanche, S, Sommerfelt, H, Rekacewicz, C, van de Perre, P, and Vallo, Roselyne
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[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology - Abstract
The efficacy of infant peri-exposure prophylaxis (PreP) to prevent HIV-1 postnatal transmission has never been assessed for the entirerecommended period of breastfeeding (12 months).The ANRS 12174 study is a randomised controlled trial comparing the efficacy and safety of lopinavir/ritonavir versus lamivudine to preventHIV-1 postnatal transmission in breastfeeding children born to HIV-1-infected mothers not eligible for ART (CD4 count above 350cells/mL) during breastfeeding (maximum 50 weeks). HIV-uninfected children aged 7 days were randomised for either drug in a 1:1 ratio.Infant HIV-infection status was assessed at week 6, 14, 26, 38 and 50 using HIV-1 DNA PCR. The study has completed enrolment in April2012 in Burkina Faso, Uganda, Zambia and South Africa. We report the current postnatal HIV-1 transmission rate and HIV-1 free survivalin the cohort among children aged 50 weeks or more in July 2012.By the end of July 2012, of 1273 children enrolled in the trial, 788 were aged 50 weeks or older. During this period, 8 transmissions occurredrepresenting a cumulative transmission rate of 1.1% (95%CI: 0.6-2.2). Interestingly, 6/8 transmissions occurred after 6 months ofbreastfeeding. Overall, 188 severe adverse events (grade 3 or more, DAIDS classification) and 22 deaths were identified. None were consideredattributable to the study drugs. The overall cumulative mortality was 3.0% (95%CI: 2.0-4.5) and HIV-1-free survival was 96.0%(95%CI: 94.3-97.2).Infant PreP is an efficacious strategy that could contribute to the elimination of HIV-1 transmission by breastfeeding.
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- 2013
11. Performance of modified WHO presumptive criteria for diagnosis of HIV infection in children
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Mutesu-Kapembwa, K, Andrews, B, Kapembwa, K, Chi, BH, Banda, Y, Mulenga, V, and Kankasa, C
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Background: Making a diagnosis of HIV infection in children aged less than 18 months remains a challenge in low resource settings like Zambia due to the limited availability of gold standard testing with HIV DNA PCR. Clinicians in rural areas have to depend on clinical diagnosis to start HAART asthey wait for the dry blood spot (DBS) for DNAPCR results sent from the urban centers.Methods: This descriptive cross-sectional study was performed at the University Teaching Hospital, Lusaka, Zambia. 299 HIV-exposed children aged less than 18 months were enrolled following a consent procedure. Patients were evaluated for HIV infection based on the World Health Organization's presumptive diagnostic criteria (WHO-PDC), integrated management of childhood illnesses (IMCI) criteria, select physical exam abnormalities, and CD4% and findings were compared with HIVDNAPCR results.Results: Of the 299 exposed patients analyzed, 111(37%) were found to be HIV-positive by DNA PCR. The median CD4% in the infected children was 18%. WHO-PDC used on its own had 23% sensitivity (95% CI 17-32%) and 93% specificity (88-96%), respectively, whereas IMCI criterion had 10% sensitivity (6-17%) and 97% specificity (94-99%), respectively. Multivariate analysis was used to identify the most sensitive predictors when combined with the WHO-PDC and IMCI criterion. WHO-PDC with CD4% improved the sensitivity to 77% (68-83%) with a specificity of 83% (77-88%), positive predictive value (PPV) of 73% (64-80%) and negative predictive value (NPV) of 86% (80-90%). IMCI with CD4% improved sensitivity to 80% (71-87%) with a specificity of 88% (82-92%), PPV 78% (69-85%) and NPV 89% (84-93%). The addition of individual physical exam findings without CD4% improved the sensitivity of WHOPDC only modestly. When the WHO-PDC, weight
- Published
- 2012
12. Effect of 7 days of phenytoin on the pharmacokinetics of and the development of resistance to single-dose nevirapine for perinatal HIV prevention: a randomized pilot trial
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Fillekes, Q., Muro, E.P., Chunda, C., Aitken, S., Kisanga, E.R., Kankasa, C., Thomason, M.J., Gibb, D.M., Walker, A.S., Burger, D.M., Fillekes, Q., Muro, E.P., Chunda, C., Aitken, S., Kisanga, E.R., Kankasa, C., Thomason, M.J., Gibb, D.M., Walker, A.S., and Burger, D.M.
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Contains fulltext : 125375.pdf (publisher's version ) (Open Access), OBJECTIVES: To confirm whether 7 days of phenytoin, an enzyme inducer, would decrease the elimination half-life of single-dose nevirapine and to investigate its effect on the development of nevirapine resistance in pregnant, HIV-infected women. METHODS: In a pharmacokinetic pilot trial (NCT01187719), HIV-infected, antiretroviral (ARV)-naive pregnant women >/=18 years old from Zambia and Tanzania and with CD4 cell counts >350 cells/mm(3) were randomized 1 : 1 to a control (zidovudine pre-delivery, single-dose nevirapine/zidovudine/lamivudine at delivery and zidovudine/lamivudine for 7 days post-delivery) or an intervention (control plus 184 mg of phenytoin once daily for 7 days post-delivery) group. Primary endpoints were the pharmacokinetics of and resistance to nevirapine. RESULTS: Thirty-five and 37 women were allocated to the control and intervention groups, with median (IQR) ages of 27 (23-31) and 27 (23-33) years, respectively. Twenty-three and 23 women had detectable nevirapine levels at delivery and subsequent samples in the control and the intervention groups, respectively. Geometric mean (GM) (95% CI) plasma levels of nevirapine at delivery were 1.02 (0.58-1.78) mg/L and 1.14 (0.70-1.86) mg/L in the control and intervention groups, respectively (P = 0.76). One week after delivery, 0/23 (0%) and 15/22 (68%) control and intervention mothers, respectively, had undetectable levels of nevirapine (<0.05 mg/L; P<0.001). One week later, the figures were 10/21 (48%) and 18/19 (95%) mothers, respectively (P = 0.002). The GM (95% CI) half-life of nevirapine was 63.2 (52.8-75.7) versus 25.5 (21.6-30.1) h in the control group versus the intervention group (P < 0.001). New nevirapine mutations were found in 0/20 (0%) intervention-group mothers versus 1/21 (5%) control-group mothers. Overall, there was no difference in adverse events reported between the control and intervention arms (P > 0.28). CONCLUSIONS: Adding 7 days of an enzyme inducer to single-dose nevirapine to
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- 2013
13. Pharmacokinetics of nevirapine in HIV-infected infants weighing 3 kg to less than 6 kg taking paediatric fixed dose combination tablets.
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Fillekes, Q., Mulenga, V., Kabamba, D., Kankasa, C., Thomason, M.J., Cook, A., Ferrier, A., Chintu, C., Walker, A.S., Gibb, D.M., Burger, D.M., Fillekes, Q., Mulenga, V., Kabamba, D., Kankasa, C., Thomason, M.J., Cook, A., Ferrier, A., Chintu, C., Walker, A.S., Gibb, D.M., and Burger, D.M.
- Abstract
Item does not contain fulltext, OBJECTIVES: : To evaluate pharmacokinetics of nevirapine, lamivudine and stavudine in HIV-infected Zambian infants receiving fixed dose combination (FDC) antiretroviral tablets (Triomune Baby). DESIGN: : Phase I/II study. METHODS: : Sixteen HIV-infected children at least 1 month, weighing 3 kg to less than 6 kg were enrolled. Blood was sampled at t = 0, 2, 6 and 12 h after observed intake of one FDC tablet (50 mg nevirapine, 6 mg stavudine, 30 mg lamivudine) 4 weeks after starting treatment. Safety and viral load response over 48 weeks were determined. RESULTS: : The median [interquartile range (IQR)] age, body weight and daily nevirapine dose in 15 included children (eight girls) were 4.8 (4.2, 8.4) months, 5.3 (4.3, 5.5) kg and 348 (326 385) mg/m, respectively. The median (IQR) nevirapine area under the concentration-time curve (AUC0-12 h), Cmax and C12 h were 70 (56, 104) h mg/l, 7.5 (6.2, 10) mg/l, and 4.3 (2.9, 6.9) mg/l, respectively. Values were on average higher than reported in adults, but approximately 20% lower than previously reported in children weighing at least 6 kg. Four of 15 (27%) children had a subtherapeutic nevirapine C12 h (defined as <3.0 mg/l) compared to only three of 63 (5%) children weighing at least 6 kg (P = 0.02), whereas children aged less than 5 months [three of six (50%)] may have the highest risk for subtherapeutic nevirapine C12 h (P = 0.24). No association was found between viral load values and nevirapine plasma pharmacokinetic parameters (P > 0.3). Stavudine-lamivudine pharmacokinetic parameters were broadly comparable to heavier children. CONCLUSION: : Exposure to nevirapine in African, HIV-infected infants with low body weight taking FDC tablets appears on average to be adequate, but due to large intersubject variability a relatively high proportion had subtherapeutic nevirapine C12 h levels, particularly those aged less than 5 months.
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- 2012
14. Limited sampling models to predict the pharmacokinetics of nevirapine, stavudine, and lamivudine in HIV-infected children treated with pediatric fixed-dose combination tablets.
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Burger, D.M., Ewings, F., Kabamba, D., L'homme, R.F.A., Mulenga, V., Kankasa, C., Thomason, M., Gibb, D.M., Chintu, C., Walker, A.S., Burger, D.M., Ewings, F., Kabamba, D., L'homme, R.F.A., Mulenga, V., Kankasa, C., Thomason, M., Gibb, D.M., Chintu, C., and Walker, A.S.
- Abstract
1 juni 2010, Contains fulltext : 87250.pdf (publisher's version ) (Closed access), Full 12-hour pharmacokinetic profiles of nevirapine, stavudine, and lamivudine in HIV-infected children taking fixed-dose combination antiretroviral tablets have been reported previously by us. Further studies with these formulations could benefit from less-intensive pharmacokinetic sampling. Data from 65 African children were used to relate area under the plasma concentration versus time curve over 12 hours (AUC) to plasma concentrations of nevirapine, stavudine, or lamivudine at times t = 0, 1, 2, 4, 6, 8, and 12 hours after intake using linear regression. Limited sampling models were developed using leave-one-out crossvalidation. The predictive performance of each model was evaluated using the mean relative prediction error (mpe%) as an indicator of bias and the root mean squared relative prediction error (rmse%) as a measure of precision. A priori set criteria to accept a limited sampling model were: 95% confidence limit of the mpe% should include 0, rmse% less than 10%, a high correlation coefficient, and as few (convenient) samples as possible. Using only one sample did not lead to acceptable AUC predictions for stavudine or lamivudine, although the 6-hour sample was acceptable for nevirapine (mpe%: -0.8%, 95% confidence interval: -2.2 to +0.6); rmse%: 5.8%; r: 0.98). Using two samples, AUC predictions for stavudine and lamivudine improved considerably but did not meet the predefined acceptance criteria. Using three samples (1, 2, 6 hours), an accurate and precise limited sampling model for stavudine AUC (mpe%: -0.6%, 95% confidence interval: -2.2 to +1.0; rmse%: 6.5%; r: 0.98) and lamivudine AUC (mpe%: -0.3%, 95% confidence interval: -1.7 to +1.1; rmse%: 5.6%; r: 0.99) was found; this model was also highly accurate and precise for nevirapine AUC (mpe%: -0.2%, 95% confidence interval: -1.0 to +0.7; rmse%: 3.4%; r: 0.99). A limited sampling model using three time points (1, 2, 6 hours) can be used to predict nevirapine, stavudine, and lamivudine AUC accurately
- Published
- 2010
15. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets.
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L'homme, R.F.A., Kabamba, D., Ewings, F.M., Mulenga, V., Kankasa, C., Thomason, M.J., Walker, A.S., Chintu, C., Burger, D.M., Gibb, D.M., L'homme, R.F.A., Kabamba, D., Ewings, F.M., Mulenga, V., Kankasa, C., Thomason, M.J., Walker, A.S., Chintu, C., Burger, D.M., and Gibb, D.M.
- Abstract
Contains fulltext : 71038.pdf (publisher's version ) (Closed access), OBJECTIVE: Triomune Baby and Junior have been developed in response to the urgent need for appropriate paediatric fixed-dose combination antiretroviral tablets, with higher nevirapine to stavudine and lamivudine ratios than adult tablets, in accordance with paediatric recommendations. We determined whether this ratio results in optimal exposure in the target population. METHODS: Seventy-one Zambian children were treated with Triomune Baby or Junior dosed according to weight bands. After 4 weeks or more, a 12-h pharmacokinetic curve was recorded. Antiretroviral plasma concentrations were assayed by high-performance liquid chromatography. RESULTS: Six children were excluded because of poor adherence. Of the remaining 65, 24 (37%) were female, 24 (37%) weighed less than 15 kg and most were malnourished. Mean (range) nevirapine C12h, Cmax and AUC12h of 6.0 (1.4, 16.9) mg/l, 10.0 (3.8, 22.5) mg/l and 94.4 (32.1, 232) mg/l per hour were higher than those reported in adults. Nevirapine C12h was subtherapeutic (< 3.0 mg/l) in four children (6%). Mean stavudine and lamivudine C12h, Cmax, AUC12h (< 0.015 mg/l, 0.45 mg/l, 1.05 mg/l per hour and 0.09 mg/l, 1.33 mg/l, 5.42 mg/l per hour) were comparable to adults. There was no evidence of a difference in nevirapine AUC12h across weight bands (P = 0.2), whereas the difference in stavudine (P = 0.0003) and lamivudine AUC12h (P = 0.01) was driven by the single weight band with unequal dosing. CONCLUSION: Nevirapine concentrations were higher but more variable than in adults; the pharmacokinetic parameters of stavudine and lamivudine were comparable to adults. As nevirapine underdosing is of greater concern than overdosing, the Triomune Baby and Junior ratio appears to be appropriate for children weighing 6 kg and over. Further research is required for children under 6 kg.
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- 2008
16. Effect of 7 days of phenytoin on the pharmacokinetics of and the development of resistance to single-dose nevirapine for perinatal HIV prevention: a randomized pilot trial
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Fillekes, Q., primary, Muro, E. P., additional, Chunda, C., additional, Aitken, S., additional, Kisanga, E. R., additional, Kankasa, C., additional, Thomason, M. J., additional, Gibb, D. M., additional, Walker, A. S., additional, and Burger, D. M., additional
- Published
- 2013
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- View/download PDF
17. HIV-1 Concentrations in Human Breast Milk Before and After Weaning
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Kuhn, L., primary, Kim, H.-Y., additional, Walter, J., additional, Thea, D. M., additional, Sinkala, M., additional, Mwiya, M., additional, Kankasa, C., additional, Decker, D., additional, and Aldrovandi, G. M., additional
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- 2013
- Full Text
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18. P02-07. High concentrations of interleukin-15 and low concentrations of CCL5 in breast milk are associated with protection against postnatal HIV transmission
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Walter, J, primary, Ghosh, MK, additional, Kuhn, L, additional, Semrau, K, additional, Sinkala, M, additional, Kankasa, C, additional, Thea, DM, additional, and Aldrovandi, GM, additional
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- 2009
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19. Role of breastfeeding cessation in mediating the relationship between maternal HIV disease stage and increased child mortality among HIV-exposed uninfected children
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Fox, M. P, primary, Brooks, D. R, additional, Kuhn, L., additional, Aldrovandi, G., additional, Sinkala, M., additional, Kankasa, C., additional, Horsburgh, R., additional, and Thea, D. M, additional
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- 2008
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20. Early Childhood Infection by Human Herpesvirus 8 in Zambia and the Role of Human Immunodeficiency Virus Type 1 Coinfection in a Highly Endemic Area
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Minhas, V., primary, Crabtree, K. L., additional, Chao, A., additional, M'soka, T. J., additional, Kankasa, C., additional, Bulterys, M., additional, Mitchell, C. D., additional, and Wood, C., additional
- Published
- 2008
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21. HIV care and treatment factors associated with improved survival during TB treatment in Thailand: an observational study
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Jiang Dd, Ningsanond P, Kankasa C, Zachariah R, Organek N, Alibhai A, van Griensven J, Chasombat S, Bailey Rc, Malinga J, Tappero Jw, Hoi Hs, Akksilp S, Ruhunda A, Kittikraisak W, Bukusi Ea, Nateniyom S, Kvalsund M, Bass J, Bradbury R, Sirinak C, Cain Kp, Thanprasertsuk S, Cohen Cr, Mwiya M, Kipp We, Hwang Kp, Bostrom A, Carrico Aw, Burapat C, Jirawattanapisal T, Isichei Co, Scott N, Fischer Pr, DeSilva Mb, Mangombe C, Obure A, McCurley E, Fox K, Wells Cd, Cha Ss, Konde-Lule J, Murray Lk, McConnell Ms, Mankatittham W, Monkongdee P, Kaile T, Tseng Sh, Mock Pa, Kwena Z, Montandon M, Yang Sl, Varma Jk, Pinyopornpanich S, Siangphoe U, Sattayawuthipong W, Reid T, Merry Sp, Rohrer Je, Byers Pa, Nguti R, Birbeck Gl, Malama K, Saunders D, Rasschaert F, Semrau K, Thea Dm, Yuktanont P, Shiboski S, Chomba E, Lertpiriyasuwat C, and Bolton P
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Program evaluation ,Adult ,Male ,Economic growth ,Time Factors ,Adolescent ,Anti-HIV Agents ,Population ,Antitubercular Agents ,Developing country ,HIV Infections ,lcsh:Infectious and parasitic diseases ,Cohort Studies ,Young Adult ,Acquired immunodeficiency syndrome (AIDS) ,Risk Factors ,Medicine ,Humans ,lcsh:RC109-216 ,education ,Tuberculosis, Pulmonary ,Aged ,Proportional Hazards Models ,education.field_of_study ,Poverty ,AIDS-Related Opportunistic Infections ,business.industry ,Middle Aged ,medicine.disease ,Thailand ,Infectious Diseases ,Treatment Outcome ,Female ,Rural area ,business ,Developed country ,Qualitative research ,Research Article - Abstract
Background In Southeast Asia, HIV-infected patients frequently die during TB treatment. Many physicians are reluctant to treat HIV-infected TB patients with anti-retroviral therapy (ART) and have questions about the added value of opportunistic infection prophylaxis to ART, the optimum ART regimen, and the benefit of initiating ART early during TB treatment. Methods We conducted a multi-center observational study of HIV-infected patients newly diagnosed with TB in Thailand. Clinical data was collected from the beginning to the end of TB treatment. We conducted multivariable proportional hazards analysis to identify factors associated with death. Results Of 667 HIV-infected TB patients enrolled, 450 (68%) were smear and/or culture positive. Death during TB treatment occurred in 112 (17%). In proportional hazards analysis, factors strongly associated with reduced risk of death were ART use (Hazard Ratio [HR] 0.16; 95% confidence interval [CI] 0.07–0.36), fluconazole use (HR 0.34; CI 0.18–0.64), and co-trimoxazole use (HR 0.41; CI 0.20–0.83). Among 126 patients that initiated ART after TB diagnosis, the risk of death increased the longer that ART was delayed during TB treatment. Efavirenz- and nevirapine-containing ART regimens were associated with similar rates of adverse events and death. Conclusion Among HIV-infected patients living in Thailand, the single most important determinant of survival during TB treatment was use of ART. Controlled clinical trials are needed to confirm our findings that early ART initiation improves survival and that the choice of non-nucleoside reverse transcriptase inhibitor does not.
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- 2009
22. Molecularly Cloned SHIV-1157ipd3N4: a Highly Replication- Competent, Mucosally Transmissible R5 Simian-Human Immunodeficiency Virus Encoding HIV Clade Cenv
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Song, R. J., primary, Chenine, A.-L., additional, Rasmussen, R. A., additional, Ruprecht, C. R., additional, Mirshahidi, S., additional, Grisson, R. D., additional, Xu, W., additional, Whitney, J. B., additional, Goins, L. M., additional, Ong, H., additional, Li, P.-L., additional, Shai-Kobiler, E., additional, Wang, T., additional, McCann, C. M., additional, Zhang, H., additional, Wood, C., additional, Kankasa, C., additional, Secor, W. E., additional, McClure, H. M., additional, Strobert, E., additional, Else, J. G., additional, and Ruprecht, R. M., additional
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- 2006
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23. Does Severity of HIV Disease in HIV-Infected Mothers Affect Mortality and Morbidity among Their Uninfected Infants?
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Kuhn, L., primary, Kasonde, P., additional, Sinkala, M., additional, Kankasa, C., additional, Semrau, K., additional, Scott, N., additional, Tsai, W.-Y., additional, Vermund, S. H., additional, Aldrovandi, G. M., additional, and Thea, D. M., additional
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- 2005
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24. Epidemiological characteristics of human herpesvirus‐8 infection in a large population of antenatal women in Zambia
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Klaskala, W., primary, Brayfield, B.P., additional, Kankasa, C., additional, Bhat, G., additional, West, J.T., additional, Mitchell, C.D., additional, and Wood, Charles, additional
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- 2004
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25. Perinatal Transmission of Kaposi's Sarcoma Associated Herpesvirus (KSHV or HHV-8).
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MANTINA, H., primary, BHAT, G. J., additional, KANKASA, C., additional, MITCHELL, C., additional, KLASKALA, W., additional, and WOOD, C., additional
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- 1999
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26. Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia.
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Bolton-Moore C, Mubiana-Mbewe M, Cantrell RA, Chintu N, Stringer EM, Chi BH, Sinkala M, Kankasa C, Wilson CM, Wilfert CM, Mwango A, Levy J, Abrams EJ, Bulterys M, Stringer JS, Bolton-Moore, Carolyn, Mubiana-Mbewe, Mwangelwa, Cantrell, Ronald A, Chintu, Namwinga, and Stringer, Elizabeth M
- Abstract
Context: The Zambian Ministry of Health provides pediatric antiretroviral therapy (ART) at primary care clinics in Lusaka, where, despite scale-up of perinatal prevention efforts, many children are already infected with the human immunodeficiency virus (HIV).Objective: To report early clinical and immunologic outcomes of children enrolled in the pediatric treatment program.Design, Setting, and Patients: Open cohort assessment using routinely collected clinical and outcome data from an electronic medical record system in use at 18 government primary health facilities in Lusaka, Zambia. Care was provided primarily by nurses and clinical officers ("physician extenders" akin to physician assistants in the United States). Patients were children (<16 years of age) presenting for HIV care between May 1, 2004, and June 29, 2007.Intervention: Three-drug ART (zidovudine or stavudine plus lamivudine plus nevirapine or efavirenz) for children who met national treatment criteria.Main Outcome Measures: Survival, weight gain, CD4 cell count, and hemoglobin response.Results: After enrollment of 4975 children into HIV care, 2938 (59.1%) started ART. Of those initiating ART, the median age was 81 months (interquartile range, 36-125), 1531 (52.1%) were female, and 2087 (72.4%) with World Health Organization stage information were in stage III or IV. At the time of analysis, 158 children (5.4%) had withdrawn from care and 382 (13.0%) were at least 30 days late for follow-up. Of the remaining 2398 children receiving ART, 198 (8.3%) died over 3018 child-years of follow-up (mortality rate, 6.6 deaths per 100 child-years; 95% confidence interval [CI], 5.7-7.5); of these deaths, 112 (56.6%) occurred within 90 days of therapy initiation (early mortality rate, 17.4/100 child-years; post-90-day mortality rate, 2.9/100 child-years). Mortality was associated with CD4 cell depletion, lower weight-for-age, younger age, and anemia in multivariate analysis. The mean CD4 cell percentage at ART initiation among the 1561 children who had at least 1 repeat measurement was 12.9% (95% CI, 12.5%-13.3%) and increased to 23.7% (95% CI, 23.1%-24.3%) at 6 months, 27.0% (95% CI, 26.3%-27.6%) at 12 months, 28.0% (95% CI, 27.2%-28.8%) at 18 months, and 28.4% (95% CI, 27.4%-29.4%) at 24 months.Conclusions: Care provided by clinicians such as nurses and clinical officers can result in good outcomes for HIV-infected children in primary health care settings in sub-Saharan Africa. Mortality during the first 90 days of therapy is high, pointing to a need for earlier intervention. [ABSTRACT FROM AUTHOR]- Published
- 2007
27. Distribution of Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 in maternal saliva and breast milk in Zambia: implications for transmission [corrected] [published erratum appears in J INFECT DIS 2004 Sep 15;190(6):1202].
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Brayfield BP, Kankasa C, West JT, Muyanga J, Bhat G, Klaskala W, Mitchell CD, and Wood C
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BACKGROUND: The seroprevalence of Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) in sub-Saharan Africa suggests that multiple routes of transmission exist. In the present study, we examined 2 possible routes of mother-to-child transmission, through breast milk and saliva, during the first 6 months after delivery. METHODS: The prevalence of HHV-8 DNA in the breast-milk cells (n=75), milk supernatant (n=56), colostrum (n=2), and saliva cells (n=65) of HHV-8-seropositive mothers who recently gave birth was examined. Polymerase chain reaction analysis was performed for the detection of HHV-8 in cross-sectional samples isolated at 2, 4, and 6 months after delivery. RESULTS: None of the 75 breast-milk samples but 2 of the colostrum samples that were analyzed contained HHV-8 DNA at a limit of detection of approximately 1 HHV-8 copy/10(4) cellular genomes, whereas Epstein-Barr virus DNA and HIV-1 DNA were detected in 16 and 22 samples, respectively. Analysis of 65 saliva cell samples, which were obtained from mothers who also provided milk samples, revealed that 19 of the samples had detectable HHV-8 DNA. Viral DNA was found at all time points, but the presence of viral DNA in saliva was independent of maternal HIV-1 serostatus (chi 2=0.33; P=.57). CONCLUSIONS: Our findings demonstrate the lack of HHV-8 DNA in the breast milk of seropositive mothers, and they suggest that contact with breast milk is not a likely source of horizontal transmission of virus to infants in sub-Saharan Africa. Copyright © 2004 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]
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- 2004
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28. α-Defensins in the prevention of HIV transmission among breastfed infants
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Kuhn, L., Daria Trabattoni, Kankasa, C., Semrau, K., Kasonde, P., Lissoni, F., Sinkala, M., Ghosh, M., Vwalika, C., Aldrovandi, G. M., Thea, D. M., and Clerici, M.
29. Lopinavir/Ritonavir versus Lamivudine peri-exposure prophylaxis to prevent HIV-1 transmission by breastfeeding: the PROMISE-PEP trial Protocol ANRS 12174
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Nagot Nicolas, Kankasa Chipepo, Meda Nicolas, Hofmeyr Justus, Nikodem Cheryl, Tumwine James K, Karamagi Charles, Sommerfelt Halvor, Neveu Dorine, Tylleskär Thorkild, and Van de Perre Philippe
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Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Postnatal transmission of HIV-1 through breast milk remains an unsolved challenge in many resource-poor settings where replacement feeding is not a safe alternative. WHO now recommends breastfeeding of infants born to HIV-infected mothers until 12 months of age, with either maternal highly active antiretroviral therapy (HAART) or peri-exposure prophylaxis (PEP) in infants using nevirapine. As PEP, lamivudine showed a similar efficacy and safety as nevirapine, but with an expected lower rate of resistant HIV strains emerging in infants who fail PEP, and lower restrictions for future HIV treatment. Lopinavir/ritonavir (LPV/r) is an attractive PEP candidate with presumably higher efficacy against HIV than nevirapine or lamivudine, and a higher genetic barrier to resistance selection. It showed an acceptable safety profile for the treatment of very young HIV-infected infants. The ANRS 12174 study aims to compare the risk of HIV-1 transmission during and safety of prolonged infant PEP with LPV/r (40/10 mg twice daily if 2-4 kg and 80/20 mg twice daily if >4 kg) versus Lamivudine (7,5 mg twice daily if 2-4 kg, 25 mg twice daily if 4-8 kg and 50 mg twice daily if >8 kg) from day 7 until one week after cessation of BF (maximum 50 weeks of prophylaxis) to prevent postnatal HIV-1 acquisition between 7 days and 50 weeks of age. Methods The ANRS 12174 study is a multinational, randomised controlled clinical trial conducted on 1,500 mother-infant pairs in Burkina Faso, South Africa, Uganda and Zambia. We will recommend exclusive breastfeeding (EBF) until 26th week of life and cessation of breastfeeding at a maximum of 49 weeks in both trial arms. HIV-uninfected infants at day 7 (± 2 days) born to HIV-1 infected mothers not eligible for HAART who choose to breastfeed their infants. The primary endpoint is the acquisition of HIV-1 (as assessed by HIV-1 DNA PCR) between day 7 and 50 weeks of age. Secondary endpoints are safety (including resistance, adverse events and growth) until 50 weeks and HIV-1-free survival until 50 weeks. Discussion This study will provide a new evidence-based intervention to support HIV-1-infected women not eligible for HAART to safely breastfeed their babies. Trial registration number (http://www.clinicaltrials.gov) NCT00640263
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- 2012
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30. Pregnancy loss and role of infant HIV status on perinatal mortality among HIV-infected women
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Kim Hae-Young, Kasonde Prisca, Mwiya Mwiya, Thea Donald M, Kankasa Chipepo, Sinkala Moses, Aldrovandi Grace, and Kuhn Louise
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Perinatal mortality ,Infant mortality ,Risk factors ,Adverse pregnancy outcome ,HIV infection ,Vertical transmission ,Pediatrics ,RJ1-570 - Abstract
Abstract Background HIV-infected women, particularly those with advanced disease, may have higher rates of pregnancy loss (miscarriage and stillbirth) and neonatal mortality than uninfected women. Here we examine risk factors for these adverse pregnancy outcomes in a cohort of HIV-infected women in Zambia considering the impact of infant HIV status. Methods A total of 1229 HIV-infected pregnant women were enrolled (2001–2004) in Lusaka, Zambia and followed to pregnancy outcome. Live-born infants were tested for HIV by PCR at birth, 1 week and 5 weeks. Obstetric and neonatal data were collected after delivery and the rates of neonatal ( Results The ratio of miscarriage and stillbirth per 100 live-births were 3.1 and 2.6, respectively. Higher maternal plasma viral load (adjusted odds ratio [AOR] for each log10 increase in HIV RNA copies/ml = 1.90; 95% confidence interval [CI] 1.10–3.27) and being symptomatic were associated with an increased risk of stillbirth (AOR = 3.19; 95% CI 1.46–6.97), and decreasing maternal CD4 count by 100 cells/mm3 with an increased risk of miscarriage (OR = 1.25; 95% CI 1.02–1.54). The neonatal mortality rate was 4.3 per 100 increasing to 6.3 by 70 days. Intrauterine HIV infection was not associated with neonatal morality but became associated with mortality through 70 days (adjusted hazard ratio = 2.76; 95% CI 1.25–6.08). Low birth weight and cessation of breastfeeding were significant risk factors for both neonatal and early mortality independent of infant HIV infection. Conclusions More advanced maternal HIV disease was associated with adverse pregnancy outcomes. Excess neonatal mortality in HIV-infected women was not primarily explained by infant HIV infection but was strongly associated with low birth weight and prematurity. Intrauterine HIV infection contributed to mortality as early as 70 days of infant age. Interventions to improve pregnancy outcomes for HIV-infected women are needed to complement necessary therapeutic and prophylactic antiretroviral interventions.
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- 2012
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31. Effect of using HIV and infant feeding counselling cards on the quality of counselling provided to HIV positive mothers: a cluster randomized controlled trial
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Babaniyi Olusegun, Kankasa Chipepo, Katepa-Bwalya Mary, and Siziya Seter
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infant feeding ,breastfeeding ,young children feeding ,HIV ,counselling cards ,Pediatrics ,RJ1-570 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Counselling human immunodeficiency virus (HIV) positive mothers on safer infant and young child feeding (IYCF) options is an important component of programmes to prevent mother to child transmission of HIV, but the quality of counselling is often inadequate. The aim of this study was to determine the effect the World Health Organization HIV and infant feeding cards on the quality of counselling provided to HIV positive mothers by health workers about safer infant feeding options. Method This was a un-blinded cluster-randomized controlled field trial in which 36 primary health facilities in Kafue and Lusaka districts in Zambia were randomized to intervention (IYCF counselling with counselling cards) or non- intervention arm (IYCF counselling without counselling cards). Counselling sessions with 10 HIV positive women attending each facility were observed and exit interviews were conducted by research assistants. Results Totals of 180 women in the intervention group and 180 women in the control group were attended to by health care providers and interviewed upon exiting the health facility. The health care providers in the intervention facilities more often discussed the advantages of disclosing their HIV status to a household member (RR = 1.46, 95% CI [1.11, 1.92]); used visual aids in explaining the risk of HIV transmission through breast milk (RR = 4.65, 95% CI [2.28, 9.46]); and discussed the advantages and disadvantages of infant feeding options for HIV positive mothers (all p values < 0.05). The differences also included exploration of the home situation (p < 0.05); involving the partner in the process of choosing a feeding option (RR = 1.38, 95% CI [1.09, 1.75]); and exploring how the mother will manage to feed the baby when she is at work (RR = 2.82, 95% CI [1.70, 4.67]). The clients in the intervention group felt that the provider was more caring and understanding (RR = 1.81, 95% CI [1.19, 2.75]). Conclusion The addition of counselling cards to the IYCF counselling session for HIV positive mothers were a valuable aid to counselling and significantly improved the quality of the counselling session.
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- 2011
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32. Cost of individual peer counselling for the promotion of exclusive breastfeeding in Uganda
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Nankunda Jolly, Kankasa Chipepo, Nkonki Lungiswa, Chola Lumbwe, Tumwine James, Tylleskar Thorkild, and Robberstad Bjarne
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Medicine (General) ,R5-920 - Abstract
Abstract Background Exclusive breastfeeding (EBF) for 6 months is the recommended form of infant feeding. Support of mothers through individual peer counselling has been proved to be effective in increasing exclusive breastfeeding prevalence. We present a costing study of an individual peer support intervention in Uganda, whose objective was to raise exclusive breastfeeding rates at 3 months of age. Methods We costed the peer support intervention, which was offered to 406 breastfeeding mothers in Uganda. The average number of counselling visits was about 6 per woman. Annual financial and economic costs were collected in 2005-2008. Estimates were made of total project costs, average costs per mother counselled and average costs per peer counselling visit. Alternative intervention packages were explored in the sensitivity analysis. We also estimated the resources required to fund the scale up to district level, of a breastfeeding intervention programme within a public health sector model. Results Annual project costs were estimated to be US$56,308. The largest cost component was peer supporter supervision, which accounted for over 50% of total project costs. The cost per mother counselled was US$139 and the cost per visit was US$26. The cost per week of EBF was estimated to be US$15 at 12 weeks post partum. We estimated that implementing an alternative package modelled on routine public health sector programmes can potentially reduce costs by over 60%. Based on the calculated average costs and annual births, scaling up modelled costs to district level would cost the public sector an additional US$1,813,000. Conclusion Exclusive breastfeeding promotion in sub-Saharan Africa is feasible and can be implemented at a sustainable cost. The results of this study can be incorporated in cost effectiveness analyses of exclusive breastfeeding promotion programmes in sub-Saharan Africa.
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- 2011
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33. Primary gamma-herpesviral infection in Zambian children
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Mitchell Charles D, Kankasa Chipepo, Crabtree Kay L, Brayfield Brad P, Minhas Veenu, and Wood Charles
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Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background HHV-8 is closely related to Epstein-Barr virus (EBV), but the clinical presentations of these two infections in early childhood are not well understood. Also, it is not known whether infection by one virus correlates with another. Here, we compare the natural history of infection by these two viruses along with the clinical manifestations and risk factors that are associated with early childhood infection in Zambia, which is an endemic area for HHV-8. Methods This study was conducted in a cohort of 12 month old Zambian children (N = 677). Data on socio-economic status and a wide range of clinical manifestations were collected. Logistic regression was used to test for significant associations between the collected variables and HHV-8 or EBV serostatus at 12 months of age. Results We observed a significantly higher seroprevalence for EBV (58.9%) as compared to HHV-8 (13.4%). HIV-1 infected children had at a significantly higher risk of being infected with HHV-8 (Odds ratio [OR] 3.69, 95% confidence interval [CI] 1.64 - 8.32). HIV-1 infection of the mothers was a significant risk factor for increased acquisition of EBV but not HHV-8 by children (OR 1.86, 05% CI 1.20 - 2.87). Self reported rash was marginally associated with primary infection for HHV-8 and EBV. Conclusions These results suggest that there is no correlation between EBV and HHV-8 infections. Infection by one does not increase the susceptibility for the second virus. Primary HHV-8 and EBV infection in early childhood may clinically present as rash but remains largely asymptomatic and may remain undetected in this population. HIV infection in the mother or child are important risk factors that contribute to EBV or HHV-8 infection.
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- 2010
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34. Reuse of single-dose nevirapine in subsequent pregnancies for the prevention of mother-to-child HIV transmission in Lusaka, Zambia: A cohort study
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Sinkala Moses, Semrau Katherine, Kankasa Chipepo, Kuhn Louise, Walter Jan, Thea Donald M, and Aldrovandi Grace M
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Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Single-dose nevirapine (SDNVP) for the prevention of mother-to-child HIV transmission (PMTCT) results in the selection of resistance mutants among HIV-infected mothers. The effects of these mutations on the efficacy of SDNVP use in a subsequent pregnancy are not well understood. Methods We compared risks of perinatal HIV transmission between multiparous women who had previously received a dose of SDNVP (exposed) and those that had not (unexposed) and who were given SDNVP for the index pregnancy within a PMTCT clinical study. We also compared transmission risks among exposed and unexposed women who had two consecutive pregnancies within the trial. Logistic regression modeling was used to adjust for possible confounders. Results Transmission risks did not differ between 59 SDNVP-exposed and 782 unexposed women in unadjusted analysis or after adjustment for viral load and disease stage (adjusted odds ratio 0.6, 95% confidence interval [CI] 0.2 to 2.0). Among 43 women who had two consecutive pregnancies during the study, transmission risks were 7% (95% CI 1% to 19%) at both the first (unexposed) and second (exposed) delivery. The results were unchanged, if infant death was included as an outcome. Conclusion These data suggest that the efficacy of SDNVP may not be diminished when reused in subsequent pregnancies.
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- 2008
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35. 'No sister, the breast alone is not enough for my baby' a qualitative assessment of potentials and barriers in the promotion of exclusive breastfeeding in southern Zambia
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Kankasa Chipepo, Katepa-Bwalya Mary, Siziya Seter, Fjeld Eli, Moland Karen, and Tylleskär Thorkild
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Pediatrics ,RJ1-570 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Appropriate feeding practices are of fundamental importance for the survival, growth, development and health of infants and young children. The aim of the present study was to collect baseline information on current infant and young child feeding practices, attitudes and knowledge in Mazabuka, Zambia, using a qualitative approach. Methods The study was conducted in Mazabuka, 130 km south of Lusaka in Zambia in January and February in 2005. Nine focus group discussions with mothers and a total of 18 in-depth interviews with fathers, grandmothers, health staff and traditional birth attendants were performed in both rural and urban areas. Results Breastfeeding was reported to be universal, the use of pre-lacteal feeds appeared to be low, colostrum was rarely discarded, and attitudes to and knowledge about exclusive breastfeeding were generally good. However, few practised exclusive breastfeeding. The barriers revealed were: (1) the perception of insufficient milk, (2) the fear of dying or becoming too sick to be able to breastfeed, (3) convention, (4) the perception of 'bad milk' and (5) lack of knowledge on the subject. The health staff and traditional birth attendants were the most important actors in transmitting knowledge about infant feeding to the mothers. Both categories appeared to have updated knowledge on child health and were well respected in the society. Fathers and grandmothers tended to be less knowledgeable on novel subjects such as exclusive breastfeeding and often showed a negative attitude towards it. At the same time they had considerable authority over mothers and children and infant feeding decisions. The rural population was in general less educated and more prone to conventional non-exclusive feeding practices. Conclusion The message that exclusive breastfeeding (EBF) is beneficial for child health had reached the health workers and was taught to mothers. However, conventions and expectations from family members in this Zambian community were important barriers in preventing the message of EBF from being translated into practice. The deep-rooted beliefs that prohibit EBF need to be addressed in projects and campaigns promoting EBF.
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- 2008
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36. Characterization of HIV-1 subtype C envelope glycoproteins from perinatally infected children with different courses of disease
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West John T, Kankasa Chipepo, He Xiang, He Jun, Hoffmann Federico, Zhang Hong, Mitchell Charles D, Ruprecht Ruth M, Orti Guillermo, and Wood Charles
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background The causal mechanisms of differential disease progression in HIV-1 infected children remain poorly defined, and much of the accumulated knowledge comes from studies of subtype B infected individuals. The applicability of such findings to other subtypes, such as subtype C, remains to be substantiated. In this study, we longitudinally characterized the evolution of the Env V1–V5 region from seven subtype C HIV-1 perinatally infected children with different clinical outcomes. We investigated the possible influence of viral genotype and humoral immune response on disease progression in infants. Results Genetic analyses revealed that rapid progressors (infants that died in the first year of life) received and maintained a genetically homogeneous viral population throughout the disease course. In contrast, slow progressors (infants that remained clinically asymptomatic for up to four years) also exhibited low levels variation initially, but attained higher levels of diversity over time. Genetic assessment of variation, as indicated by dN/dS, showed that particular regions of Env undergo selective changes. Nevertheless, the magnitude and distribution of these changes did not segregate slow and rapid progressors. Longitudinal trends in Env V1–V5 length and the number of potential N-glycosylation sites varied among patients but also failed to discriminate between fast and slow progressors. Viral isolates from rapid progressors and slow progressors displayed no significant growth properties differences in vitro. The neutralizing activity in maternal and infant baseline plasma also varied in its effectiveness against the initial virus from the infants but did not differentiate rapid from slow progressors. Quantification of the neutralization susceptibility of the initial infant viral isolates to maternal baseline plasma indicated that both sensitive and resistant viruses were transmitted, irrespective of disease course. We showed that humoral immunity, whether passively acquired or developed de novo in the infected children, varied but was not predictive of disease progression. Conclusion Our data suggest that neither genetic variation in env, or initial maternal neutralizing activity, or the level of passively acquired neutralizing antibody, or the level of the de novo neutralization response appear to be linked to differences in disease progression in subtype C HIV-1 infected children.
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- 2006
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37. Evolution of subtype C HIV-1 Env in a slowly progressing Zambian infant
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Kankasa Chipepo, He Xiang, He Jun, Hoffmann Federico, Zhang Hong, Ruprecht Ruth, West John T, Orti Guillermo, and Wood Charles
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background Given the high prevalence of mother to child infection, the development of a better understanding of African subtype C HIV-1 transmission and natural evolution is of significant importance. In this study, we genotypically and phenotypically characterized subtype C viruses isolated over a 67-month follow-up period from an in utero-infected Zambian infant. Changes in genotype and phenotype were correlated to alterations of the host humoral immune response. Results A comparison of baseline maternal and infant samples indicated that the infant sequences are monophyletic and contain a fraction of the diversity observed in the mother. This finding suggests that selective transmission occurred from mother to child. Peaks in infant HIV-1 Env genetic diversity and divergence were noted at 48 months, but were not correlated with changes in co-receptor usage or syncytia phenotype. Phylogenetic analyses revealed an accumulation of mutations over time, as well as the reappearance of ancestral lineages. In the infant C2-V4 region of Env, neither the median number of putative N-glycosylation sites or median sequence length showed consistent increases over time. The infant possessed neutralizing antibodies at birth, but these decreased in effectiveness or quantity with time. De novo humoral responses were detected in the child after 12 months, and corresponded with an increase in Env diversity. Conclusion Our study demonstrates a correlation between HIV-1 Env evolution and the humoral immune response. There was an increase in genetic diversification in the infant viral sequences after 12 months, which coincided with increases in neutralizing antibody titers. In addition, episodes of viral growth and successive immune reactions in the first 5–6 years were observed in this slow progressor infant with delayed onset of AIDS. Whether this pattern is typical of slow progressing subtype C HIV-1 infected infant needs to be further substantiated.
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- 2005
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38. Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial.
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Chi BH, Sinkala M, Mbewe F, Cantrell RA, Kruse G, Chintu N, Aldrovandi GM, Stringer EM, Kankasa C, Safrit JT, and Stringer JS
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- 2007
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39. Combination of serological and cytokine release assays for improved diagnosis of childhood tuberculosis in Zambia (PROMISE-TB).
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Tuaillon E, Mwyia M, Bollore K, Pisoni A, Rubbo PA, Richard M, Kremer L, Tonga MMW, Chanda D, Peries M, Vallo R, Eymard-Duvernay S, D'Ottavi M, Kankasa C, de Perre PV, Moles JP, and Nagot N
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Objectives: The diagnostic gaps for childhood tuberculosis (TB) remain considerable in settings with high TB incidence and resource constraints. We established and evaluated the performance of a scoring system based on a combination of serological tests and T-cell cytokine release assays, chosen for their ability to detect immune responses indicative of TB, in a context of high prevalence of pediatric HIV infection., Methods: We enrolled 628 consecutive children aged ≤15 years, admitted for TB suspicion. Multiple cytokine levels in QuantiFERON Gold In-Tube supernatants and antigen 85B (Ag85B) antibodies were assessed in children who tested positive with either Xpert TB or mycobacterial culture. The results were compared with those of control children., Results: Among the biomarkers most strongly associated with TB, random forest classification analysis selected Ag85B antibodies, interleukin-2/interferon-γ ratio, and monokine induced by interferon-γ for the scoring system. The receiver operating characteristic curve derived from our scoring system showed an area under the curve of 0.95 (0.91-0.99), yielding 91% sensitivity and 88% specificity. The internal bootstrap validation gave the following 95% confidence intervals for the score performance: sensitivity 71%-97% and specificity 79%-99%., Conclusions: This study suggests that supplementing the QuantiFERON assay with a combination of serological and T-cell markers could enhance childhood TB screening regardless of HIV status and age. Further validation among the target population is necessary to confirm the performance of this scoring system., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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40. Evaluation of the prevention of mother-to-child transmission of HIV programs at the second immunization visit in Burkina Faso and Zambia.
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Tassembedo S, Mwiya M, Mennecier A, Kankasa C, Fao P, Molès JP, Kania D, Chunda-Liyoka C, Sakana BLD, D'Ottavi M, Taofiki AO, Rutagwera D, Wilfred-Tonga MM, Tylleskär T, Nagot N, and Van de Perre P
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- Infant, Infant, Newborn, Humans, Pregnancy, Female, Infectious Disease Transmission, Vertical prevention & control, Burkina Faso, Zambia, Cross-Sectional Studies, Immunization, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections prevention & control
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Objective: Our study aimed to assess the PMTCT indicators in Burkina Faso and Zambia using a patient-orientated innovative strategy based on the second visit in the Expanded Program on Immunization (EPI-2) visit at 6-8 weeks., Design: This was a cross sectional study., Methods: We assessed women attending EPI-2 at primary healthcare facilities in Burkina Faso and Zambia with their children about their exposure to PMTCT interventions. For women living with HIV (WLHIV), viral load was measured and their children were tested for HIV DNA using point of care devices., Results: Overall, 25 093 were enrolled from Burkina Faso and 8961 women from Zambia. Almost, all women attended at least one antenatal care visit. Among those aware of their HIV-positive status, 95.8 and 99.2% were on antiretroviral therapy (ART) in Burkina Faso and Zambia, respectively. Among WLHIV on ART, 75 and 79.2% achieved a viral load suppression (viral load <1000 copies/ml) in Burkina Faso and Zambia, respectively. Infant postnatal prophylaxis was administered from birth until EPI-2 to 60.9 and 89.7% of HIV-exposed children in Burkina Faso and Zambia, respectively. In Burkina Faso, only 60 of 192 (31.3%) of HIV-exposed children were sampled at day 42 for early infant diagnosis (EID) and 3 (1.6%) received a result by EPI-2. In Zambia, these figures were 879 of 1465 (64.0%) and 9.9% (145/1465), respectively for HIV-exposed children sampled at birth., Conclusion: This evaluation strategy at EPI-2 visit could strengthen program monitoring and help identifying gaps to be addressed on the last mile towards elimination of MTCT of HIV., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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41. Optimised prevention of postnatal HIV transmission in Zambia and Burkina Faso (PROMISE-EPI): a phase 3, open-label, randomised controlled trial.
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Kankasa C, Mennecier A, Sakana BLD, Molès JP, Mwiya M, Chunda-Liyoka C, D'Ottavi M, Tassembedo S, Wilfred-Tonga MM, Fao P, Rutagwera D, Matoka B, Kania D, Taofiki OA, Tylleskär T, Van de Perre P, and Nagot N
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- Adult, Female, Humans, Infant, Burkina Faso, Infectious Disease Transmission, Vertical prevention & control, Lamivudine therapeutic use, Mothers, Zambia epidemiology, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections prevention & control, HIV Infections epidemiology
- Abstract
Background: Transmission through breastfeeding accounts for more than half of the unacceptably high number of new paediatric HIV infections worldwide. We hypothesised that, in addition to maternal antiretroviral therapy (ART), extended postnatal prophylaxis with lamivudine, guided by point-of-care assays for maternal viral load, could reduce postnatal transmission., Methods: We did a phase 3, open-label, randomised controlled trial at four health-care facilities in Zambia and four health-care facilities in Burkina Faso. Mothers with HIV and their breastfed infants without HIV attending the second visit of the Expanded Programme of Immunisation (EPI-2; infant age 6-8 weeks) were randomly assigned 1:1 to intervention or control groups. In the intervention group, maternal viral load was measured using Xpert HIV viral load assay at EPI-2 and at 6 months, with results provided immediately. Infants whose mothers had a viral load of 1000 copies per mL or higher were started on lamivudine syrup twice per day for 12 months or 1 month after breastfeeding discontinuation. The control group followed national guidelines for prevention of postnatal transmission of HIV. The primary outcome assessed by modified intention to treat was infant HIV infection at age 12 months, with HIV DNA point-of-care testing at 6 months and at 12 months. This trial is registered with ClinicalTrials.gov (NCT03870438)., Findings: Between Dec 12, 2019 and Sept 30, 2021, 34 054 mothers were screened for HIV. Among them, 1506 mothers with HIV and their infants without HIV, including 1342 mother and infant pairs from Zambia and 164 from Burkina Faso, were eligible and randomly assigned 1:1 to the intervention (n=753) or control group (n=753). At baseline, the median age of the mothers was 30·6 years (IQR 26·0-34·7), 1480 (98·4%) of 1504 were receiving ART, and 169 (11·5%) of 1466 had a viral load ≥1000 copies/mL. There was one case of HIV transmission in the intervention group and six in the control group, resulting in a transmission incidence of 0·19 per 100 person-years (95% CI 0·005-1·04) in the intervention group and 1·16 per 100 person-years (0·43-2·53) in the control group, which did not reach statistical significance (p=0·066). HIV-free survival and serious adverse events were similar in both groups., Interpretation: Our intervention, initiated at EPI-2 and based on extended single-drug postnatal prophylaxis guided by point-of-care maternal viral load could be an important strategy for paediatric HIV elimination., Funding: The EDCTP2 programme with the support of the UK Department of Health & Social Care., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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42. Facilitators and barriers to infant post-natal HIV prophylaxis, a qualitative sub-study of the PROMISE-EPI trial in Lusaka, Zambia.
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Mennecier A, Matoka B, Wilfred-Tonga MM, Chunda-Liyoka C, Mwiya M, Nagot N, Molès JP, Van de Perre P, Kankasa C, and King R
- Subjects
- Female, Humans, Infant, Focus Groups, Qualitative Research, Zambia, HIV Infections drug therapy, HIV Infections prevention & control, Lamivudine therapeutic use, Post-Exposure Prophylaxis, Infectious Disease Transmission, Vertical prevention & control
- Abstract
Background: Infant post-natal prophylaxis (PNP) is used to prevent HIV transmission through breastfeeding. The WHO edited recommendations but so far there is no consensus on the duration of prophylaxis and the type of drug used depends on national guidelines. In Zambia, the national recommendations include a three-drug prophylaxis, composed of a dispersible combined tablet of zidovudine (AZT) and lamivudine (3TC) and an oral suspension of nevirapine (NVP) for 12 weeks or until the mother's viral load is <1,000 cp/mL. The PROMISE-EPI study, modified the PNP regimen to lamivudine only, initiated at 6 weeks and continued until 12 months to all HIV exposed uninfected infants of virally unsuppressed mothers. Our aim in this analysis was to identify barriers and facilitators to this extended PNP, the keystone toward an effective prevention., Methods: Individual interviews and focus group discussion (FGD) were conducted with PROMISE-EPI participants who had received prophylaxis for their children from the national program up to 6 weeks and then lamivudine oral solution in PROMISE-EPI study. Health care providers and PROMISE-EPI staff were also interviewed. Sessions were recorded, transcribed verbatim and translated from local languages into English. An initial code-book was designed and then adapted on the basis of the emerging themes, to allow a descriptive thematic analysis., Results: More barriers to PNP adherence were identified with triple drug prophylaxis than with lamivudine. These barriers were related to the formulation and bitter taste of AZT/3TC tablets. The ready to use formulation and sweet taste of lamivudine syrup were appreciated by mothers. Extended PNP proposed in the PROMISE-EPI study was globally well accepted and strategies were found to increase adherence. Adherence to lamivudine appeared to be better than the mothers' adherence to their own antiretroviral therapy., Conclusion: Accompanying mothers living with HIV and giving them the choice of the PNP to prevent transmission via breastfeeding (type of PNP regimen and extended PNP in non-adherent mothers), may be one of the keys to reducing the burden of pediatric HIV acquisition in low and middle income countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mennecier, Matoka, Wilfred-Tonga, Chunda-Liyoka, Mwiya, Nagot, Molès, Van de Perre, Kankasa and King.)
- Published
- 2023
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43. Impact of the COVID-19 Pandemic on Tuberculosis Testing and Treatment at a Tertiary Hospital in Zambia.
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Rosser JI, Phiri C, Bramante JT, Fwoloshi S, Kankasa C, Lungu P, Chanda R, Chipimo P, Mulenga L, Claassen CW, and Chanda D
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- Humans, Pandemics, Zambia epidemiology, Tertiary Care Centers, COVID-19, Tuberculosis diagnosis, Tuberculosis drug therapy, Tuberculosis epidemiology
- Abstract
Globally, tuberculosis (TB) testing and treatment have declined dramatically during the COVID-19 pandemic. We quantified the change in TB visits, testing, and treatment compared with a 12-month pre-pandemic baseline at the national referral hospital's TB Clinic in Lusaka, Zambia, in the first year of the pandemic. We stratified the results into early and later pandemic periods. In the first 2 months of the pandemic, the mean number of monthly TB clinic visits, prescriptions, and positive TB polymerase chain reaction (PCR) tests decreased as follow: -94.1% (95% CI: -119.4 to -68.8%), -71.4% (95% CI: -80.4 to -62.4%), and -73% (95% CI: -95.5 to -51.3%), respectively. TB testing and treatment counts rebounded in the subsequent 10 months, although the number of prescriptions and TB-PCR tests performed remained significantly lower than pre-pandemic. The COVID-19 pandemic significantly disrupted TB care in Zambia, which could have long-lasting impacts on TB transmission and mortality. Future pandemic preparedness planning should incorporate strategies developed over the course of this pandemic to safeguard consistent, comprehensive TB care.
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- 2023
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44. A Randomized Trial of Point-of-Care Early Infant Human Immunodeficiency Virus (HIV) Diagnosis in Zambia.
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Chibwesha CJ, Mollan KR, Ford CE, Shibemba A, Saha PT, Lusaka M, Mbewe F, Allmon AG, Lungu R, Spiegel HML, Mweni E, Mwape H, Kankasa C, Chi BH, and Stringer JSA
- Subjects
- Child, Early Diagnosis, HIV, Humans, Infant, Point-of-Care Testing, Zambia epidemiology, HIV Infections diagnosis, HIV Infections drug therapy, Point-of-Care Systems
- Abstract
Background: Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART)., Methods: We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory). Infants with HIV were referred for ART and followed for 12 months. Our primary outcome was defined as alive, in care, and virally suppressed at 12 months., Results: Between March 2016 and November 2018, we randomized 4000 HIV-exposed infants to POC (n=1989) or SOC (n=2011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (interquartile range: 22-30) days. Eighty-one (2%; 95% confidence interval [CI]: 1.6-2.5%) infants were diagnosed with HIV. Although ART initiation was high, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures. By 12 months, only 20 of 81 (25%; 95% CI: 15-34%) infants with HIV were alive, in care, and virally suppressed: 13 (30%; 16-43%) infants in the POC group vs 7 (19%; 6-32%) in the SOC group (RR: 1.56; .7-3.50)., Conclusions: POC EID eliminated diagnostic delays and accelerated ART initiation but did not translate into definitive improvement in 12-month outcomes. In settings where centralized EID is well functioning, POC EID is unlikely to improve pediatric HIV outcomes., Clinical Trials Registration: This trial is registered at https://clinicaltrials.gov (NCT02682810)., Competing Interests: Potential conflicts of interest. J. S. A. S. reports support from the Bill and Melinda Gates Foundation, outside the submitted work. All other authors report no potential conflicts. The authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Published
- 2022
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45. Long-Term Persistence of Mitochondrial DNA Instability in HIV-Exposed Uninfected Children during and after Exposure to Antiretroviral Drugs and HIV.
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Desquiret-Dumas V, D'Ottavi M, Monnin A, Goudenège D, Méda N, Vizeneux A, Kankasa C, Tylleskar T, Bris C, Procaccio V, Nagot N, Van de Perre P, Reynier P, and Molès JP
- Abstract
HIV-exposed uninfected (HEU) children show impaired health outcomes during childhood. A high rate of mitochondrial DNA (mtDNA) instability was reported in the blood of HEU at birth. We aimed to explore the relationship between these health outcomes and mtDNA deletions over time in a case series of 24 HEU children. MtDNA instability was assessed by deep sequencing and analyzed by eKLIPse-v2 algorithm at three time points, namely birth, 1 year, and 6 years of age. Association between mtDNA deletion and health outcomes, including growth, clinical, and neurodevelopmental parameters, were explored using univariate statistical analyses and after stratification with relevant variables. HEU children were selected with an equal male:female ratio. An elevated number of mtDNA deletions and duplications events was observed at 7 days' post-partum. Median heteroplasmy increased at one year of life and then returned to baseline by six years of age. The mtDNA instability was acquired and was not transmitted by the mother. No risk factors were significantly associated with mtDNA instability. In this small case series, we did not detect any association between any health outcome at 6 years and mtDNA instability measures. A significant effect modification of the association between the duration of maternal prophylaxis and child growth was observed after stratification with heteroplasmy rate. Genomic instability persists over time among HEU children but, despite its extension, stays subclinical at six years., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
- Published
- 2022
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46. Recurrent Severe Subclinical Mastitis and the Risk of HIV Transmission Through Breastfeeding.
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Rutagwera DG, Molès JP, Kankasa C, Mwiya M, Tuaillon E, Peries M, Nagot N, Van de Perre P, and Tylleskär T
- Subjects
- Breast Feeding, Chemokine CCL5, Chemokine CXCL10, Cytokines, Female, Humans, Interleukin-6, Interleukin-8, Retrospective Studies, Sodium, Zambia, HIV Infections epidemiology, HIV-1, Mastitis epidemiology
- Abstract
Subclinical mastitis (SCM) is an important risk factor of postnatal HIV-1 transmission that is still poorly understood. A longitudinal sub-study of the ANRS12174 trial including 270 breastfeeding mothers in Lusaka, Zambia measured sodium (Na
+ ) and potassium (K+ ) in archived paired breast milk samples collected at week 14, 26 and 38 postpartum to determine cumulative incidence of SCM and the effects of recurrent severe SCM on HIV-1 shedding in breast milk. A nested retrospective cohort study including 112 mothers was also done to determine longitudinal effects of SCM on four pro-inflammatory cytokines; IL6, IL8, IP10 and RANTES. The cumulative incidence for any SCM (Na+ /K+ ratio > 0.6) and severe SCM (Na+ /K+ ratio > 1) were 58.6% (95%CI: 52.7 - 64.5) and 27.8% (95%CI: 22.5 - 33.1), respectively. In majority of affected mothers (51.4%) severe SCM was recurrent. Both breasts were involved in 11.1%, 33.3% and 70% of the mothers with a single episode, 2 and 3 episodes respectively. In affected breasts, an episode of severe SCM resulted in steep upregulation of the four cytokines considered (IL8, IP10, RANTES and IL6) compared to: before and after the episode; contralateral unaffected breasts; and SCM negative control mothers. Recurrent severe SCM significantly increased the odds of shedding cell-free HIV-1 in breast milk (OR: 5.2; 95%CI: 1.7 - 15.6) whereas single episode of severe SCM did not (OR: 1.8; 95%CI: 0.8 - 4.2). A Na+ /K+ ratio > 1 indicative of severe SCM is an excellent indicator of breast inflammation characterized by a steep, localized and temporal upregulation of several pro-inflammatory cytokines that favor HIV-1 shedding in mature breast milk and may facilitate postnatal HIV-1 transmission through breastfeeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rutagwera, Molès, Kankasa, Mwiya, Tuaillon, Peries, Nagot, Van de Perre and Tylleskär.)- Published
- 2022
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47. Feasibility of using infant testing during immunization to estimate HIV mother-to-child-transmission rates in Zambia.
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Simbaya J, Funjika P, Moonga A, Mwale J, and Kankasa C
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- Adult, Cross-Sectional Studies, Feasibility Studies, Female, Humans, Immunization, Infant, Male, Mothers, Vaccination, Zambia epidemiology, HIV Infections epidemiology, HIV Infections prevention & control, Infectious Disease Transmission, Vertical prevention & control
- Abstract
Background: This study piloted the feasibility of infant testing in immunization services as a strategy for estimating MTCT rates among the population of HIV exposed infants at national and subnational levels in Zambia., Methods: The study recruited a cross-sectional nationally representative sample of 8042 caregiver-baby pairs in 38 high volume immunization sites in 7 towns across 3 provinces of Zambia. All mothers who brought their children below the age of one year for immunization at the study facilities were invited to participate in the study. All consenting mothers were interviewed and blood drawn from their babies for; rapid HIV antibody test to determine exposure and DNA PCR test for samples of all HIV-exposed babies to determine HIV infection., Results: Of 8042 recruited caregiver-baby pairs, 1409 (17.5%) babies were HIV-exposed. Approximately 90.2% of all mothers of HIV exposed infants reported that they attended ANC visits more than two times and facility based deliveries stood at 91.6%. Exclusive breastfeeding among HIV exposed infants reduced with increase in age of infant; it was highest at 6 weeks (82.2%) followed by 10 weeks (74.0%) and 14 weeks (58.2%). MTCT rates were relatively lower than what was reported before in subnational studies and stood at 4.7% among Penta 1 seekers, 2.8% among Penta 2 seekers, 2.1% among Penta 3 seekers and 5.0% among Measles vaccination seekers. The overall MTCT rate stood at 3.8%. About 48.1% of HIV positive babies were male compared to 51.9% females. Babies of mothers below the age of 25 years accounted for almost half (51.9%) of all HIV infected babies in the study. Reported exclusive breastfeeding among HIV positive babies was 77.8% for Penta 1 seekers, 75.0% for Penta 2 seekers and 100% for Penta 3 seekers., Conclusions: The study succeeded in estimating the MTCT rates using infant testing in immunization services, thereby demonstrating that it is feasible to use routine infant testing in immunization services as a strategy for estimating MTCT rates among the population of HIV-exposed infants in countries with high HIV burden and immunization coverage., (© 2021. The Author(s).)
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- 2021
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48. Longitudinal Follow-Up of Blood Telomere Length in HIV-Exposed Uninfected Children Having Received One Year of Lopinavir/Ritonavir or Lamivudine as Prophylaxis.
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Monnin A, Vizeneux A, Nagot N, Eymard-Duvernay S, Meda N, Singata-Madliki M, Ndeezi G, Tumwine JK, Kankasa C, Goga A, Tylleskär T, Van de Perre P, and Molès JP
- Abstract
Telomere shortening can be enhanced upon human immunodeficiency virus (HIV) infection and by antiretroviral (ARV) exposures. The aim of this study was to evaluate the acute and long-term effect on telomere shortening of two ARV prophylaxes, lopinavir/ritonavir (LPV/r) and lamivudine (3TC), administered to children who are HIV-exposed uninfected (CHEU) to prevent HIV acquisition through breastfeeding during the first year of life, and to investigate the relationship between telomere shortening and health outcomes at six years of age. We included 198 CHEU and measured telomere length at seven days of life, at week-50 and at six years (year-6) using quantitative polymerase chain reaction. At week-50, telomere shortening was observed among 44.3% of CHEU, irrespective of the prophylactic treatment. Furthermore, this telomere shortening was neither associated with poor growth indicators nor neuropsychological outcomes at year-6, except for motor abilities (MABC test n = 127, β = -3.61, 95%CI: -7.08, -0.14; p = 0.04). Safety data on telomere shortening for infant HIV prophylaxis are scarce. Its association with reduced motor abilities deserves further attention among CHEU but also HIV-infected children receiving ARV treatment.
- Published
- 2021
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49. Design and challenges of a large HIV prevention clinical study on mother-to-child transmission: ANRS 12397 PROMISE-EPI study in Zambia and Burkina Faso.
- Author
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Mennecier A, Kankasa C, Fao P, Moles JP, Eymard-Duvernay S, Mwiya M, Kania D, Chunda-Liyoka C, Sakana L, Rutagwera D, Tassembedo S, Wilfred-Tonga MM, Mosqueira B, Tylleskär T, Nagot N, and Van de Perre P
- Subjects
- Adolescent, Adult, Female, Humans, Infant, Young Adult, Burkina Faso, COVID-19 epidemiology, Cross-Sectional Studies, Pandemics, Pre-Exposure Prophylaxis methods, Research Design, SARS-CoV-2, Viral Load, Zambia, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Anti-HIV Agents administration & dosage, Anti-HIV Agents adverse effects, Anti-HIV Agents therapeutic use, Breast Feeding, HIV Infections diagnosis, HIV Infections drug therapy, HIV Infections transmission, Infectious Disease Transmission, Vertical prevention & control, Lamivudine administration & dosage, Lamivudine adverse effects, Lamivudine therapeutic use
- Abstract
Post-natal HIV infection through breastfeeding remains a challenge in many low and middle-income countries, particularly due to non-availability of alternative infant feeding options and the suboptimal Prevention of Mother to Child Transmission of HIV-1 (PMTCT) cascade implementation and monitoring. The PROMISE-EPI study aims to address the latter by identifying HIV infected mothers during an almost never-missed visit for their infant, the second extended program on immunization visit at 6-8 weeks of age (EPI-2). The study is divided into 3 components inclusive of an open-label randomized controlled trial aiming to assess the efficacy of a responsive preventive intervention compared to routine intervention based on the national PMTCT guidelines for HIV-1 uninfected exposed breastfeeding infants. The preventive intervention includes: a) Point of care testing for early infant HIV diagnosis and maternal viral load; b) infant, single-drug Pre-Exposure Prophylaxis (PrEP) (lamivudine) if mothers are virally unsuppressed. The primary outcome is HIV-transmission rate from EPI-2 to 12 months. The study targets to screen 37,000 mother/infant pairs in Zambia and Burkina Faso to identify 2000 mother/infant pairs for the clinical trial. The study design and challenges faced during study implementation are described, including the COVID-19 pandemic and the amended HIV guidelines in Zambia in 2020 (triple-drug PrEP in HIV exposed infants guided by quarterly maternal viral load). The changes in the Zambian guidelines raised several questions including the equipoise of PrEP options, the standard of care-triple-drug (control arm in Zambia) versus the study-single-drug (intervention arm). Trial registration number (www.clinicaltrials.gov): NCT03869944. Submission category: Study Design, Statistical Design, Study Protocols., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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50. Mitochondrial DNA Instability Is Common in HIV-Exposed Uninfected Newborns.
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Monnin A, Desquiret-Dumas V, Méda N, Goudenège D, Bris C, Kankasa C, Singata-Madliki M, Tylleskar T, Procaccio V, Nagot N, Van de Perre P, Reynier P, and Molès JP
- Abstract
Worldwide, one million HIV-exposed uninfected (HEU) children are born yearly, and chronic health impairments have been reported in these children. Mitochondrial DNA (mtDNA) instability and altered mtDNA content have been evidenced in these children, but an exhaustive characterization of altered mitochondrial genomes has never been reported. We applied deep mtDNA sequencing coupled to the deletion identification algorithm eKLIPse to the blood of HEU neonates ( n = 32), which was compared with healthy controls ( n = 15). Dried blood spots (DBS) from African HEU children were collected seven days after birth between November 2009 and May 2012. DBS from French healthy controls were collected at birth (or <3 days of life) in 2012 and in 2019. In contrast to the absence of mtDNA instability observed at the nucleotide level, we identified significant amounts of heteroplasmic mtDNA deletions in 75% of HEU children and in none of controls. The heteroplasmy rate of the 62 mtDNA deletions identified varied from 0.01% to up to 50%, the highest rates being broadly compatible with bioenergetic defect and clinical expression. mtDNA integrity is commonly affected in HEU neonates. The nature of the deletions suggests a mechanism related to aging or tumor-associated mtDNA instability. This child population may be at risk of additional mtDNA genetic alterations considering that they will be exposed to other mitotoxic drugs including antiretroviral or anti-tuberculosis treatment.
- Published
- 2021
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