Browsing by Author "Mubiru, Michael"
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Item Distribution of haematological and chemical pathology values among infants in Malawi and Uganda(Paediatrics and international child health, 2012) Kumwenda, Newton I.; Khonje, Tiwonge; Mipando, Linda; Nkanaunena, Kondwani; Katundu, Pauline; Lubega, Irene; Bolton, Steve; Bagenda, Danstan; Mubiru, Michael; Glenn Fowler, Mary; Taha, Taha E.; Ali, ElbireerData on paediatric reference laboratory values are limited for sub-Saharan Africa. Objective: To describe the distribution of haematological and chemical pathology values among healthy infants from Malawi and Uganda. Methods: A cross-sectional study was conducted among healthy infants, 0–6 months old, born to HIVuninfected mothers recruited from two settings in Blantyre, Malawi and Kampala, Uganda. Chemical pathology and haematology parameters were determined using standard methods on blood samples. Descriptive analyses by age-group were performed based on 2004 Division of AIDS Toxicity Table age categories. Mean values and interquartile ranges were compared by site and age-group. Results: A total of 541 infants were included altogether, 294 from Malawi and 247 from Uganda. Overall, the mean laboratory values were comparable between the two sites. Mean alkaline phosphatase levels were lower among infants aged (21 days while aspartate aminotransferase, creatinine, total bilirubin and gamma-glutamyl transferase were higher in those aged 0–7 days than in older infants. Mean haematocrit, haemoglobin and neutrophil counts were higher in the younger age-groups (,35 days) and overall were lower than US norms. Red and white blood cell counts tended to decrease after birth but increased after y2 months of age. Mean basophil counts were higher in Malawi than in Uganda in infants aged 0–1 and 2– 7 days; mean counts for eosinophils (for age groups 8–21 or older) and platelets (for all age groups) were higher in Ugandan than in Malawian infants. Absolute lymphocyte counts increased with infant age. Conclusion: The chemical pathology and haematological values in healthy infants born to HIV-uninfected mothers were comparable in Malawi and Uganda and can serve as useful reference values in these settings.Item The Impact of Maternal Highly Active Antiretroviral Therapy and Short-Course Combination Antiretrovirals for Prevention of Mother-to-Child Transmission on Early Infant Infection Rates at the Mulago National Referral Hospital in Kampala, Uganda, January 2007 to May 2009(JAIDS Journal of Acquired Immune Deficiency Syndromes, 2021) Namukwaya, Zikulah; Mudiope, Peter; Musoke, Philippa; Matovu, Joyce; Kayma, Sarah; Salmond, William; Bitarakwate, Edward; Mubiru, Michael; Maganda, Albert; Galla, Moses; Byamugisha, Josaphat; Fowler, Mary GlennEarly HIV infant diagnosis and treatment have been shown to dramatically improve survival in infants. Despite these findings, infants accessing HIV diagnosis and treatment remain low in Uganda. We describe the antiretroviral (ARV) drugs given in the Mulago Hospital prevention of mother-to-child transmission (PMTCT) program from January 2007 to May 2009 and its impact on early infant HIV infection rates. Methods: Pregnant women identified as HIV infected in the Mulago antenatal clinics received one of the following regimens: short-course ARV prophylaxis plus single-dose nevirapine (sdNVP) in labor, highly active antiretroviral therapy (HAART), or sdNVP if they presented in labor. Infants received sdNVP and zidovudine (ZDV) for 1 week. Infants HIV diagnosis was done from 6 weeks after delivery. Results: 62.3% of HIV-infected women received combination ARVs, including HAART. Early infection rates were highest among infants with no maternal ARV [36.4; 95% confidence interval (CI): 17.2 to 59.3] or only sdNVP (11.2; 95% CI: 8.1 to 14.8). Similar rates were observed for the group that took short-course ARVs, ZDV/sdNVP (4.6; 95% CI: 3.2 to 6.4), and ZDV/lamivudine/sdNVP (4.9; 95% CI: 3.1 to 7.2) and lowest rates for those that took HAART (1.7: 95% CI: 0.8 to 2.8). Overall infection rate was 5.0% (95% CI: 4.1 to 5.9). Conclusions: Findings indicate low rates of infant infection for mothers receiving combination ARVs. These findings demonstrate that provision of combination ARV for PMTCT is feasible and effective in busy referral hospital’s PMTCT programs in resource- limited settingsItem Impaired Haemophilus influenzae Type b Transplacental Antibody Transmission and Declining Antibody Avidity through the First Year of Life Represent Potential Vulnerabilities for HIV-Exposed but -Uninfected Infants(Clinical and Vaccine Immunology, 2014) Gaensbauer, James T.; Rakhola, Jeremy T.; Onyango-Makumbi, Carolyne; Mubiru, Michael; Westcott, Jamie E.; Krebs, Nancy F.; Asturias, Edwin J.; Fowler, Mary Glenn; McFarland, Elizabeth; Janoff, Edward N.To determine whether immune function is impaired among HIV-exposed but -uninfected (HEU) infants born to HIV-infected mothers and to identify potential vulnerabilities to vaccine-preventable infection, we characterized the mother-to-infant placen- tal transfer of Haemophilus influenzae type b-specific IgG (Hib-IgG) and its levels and avidity after vaccination in Ugandan HEU infants and in HIV-unexposed U.S. infants. Hib-IgG was measured by enzyme-linked immunosorbent assay in 57 Ugandan HIV- infected mothers prenatally and in their vaccinated HEU infants and 14 HIV-unexposed U.S. infants at birth and 12, 24, and 48 weeks of age. Antibody avidity at birth and 48 weeks of age was determined with 1 M ammonium thiocyanate. A median of 43% of maternal Hib-IgG was transferred to HEU infants. Although its level was lower in HEU infants than in U.S. infants at birth (P < 0.001), Hib-IgG was present at protective levels (>1.0 - g/ml) at birth in 90% of HEU infants and all U.S. infants. HEU in- fants had robust Hib-IgG responses to a primary vaccination. Although Hib-IgG levels declined from 24 to 48 weeks of age in HEU infants, they were higher than those in U.S. infants (P 0.002). Antibody avidity, comparable at birth, declined by 48 weeks of age in both populations. Early vaccination of HEU infants may limit an initial vulnerability to Hib disease resulting from impaired transplacental antibody transfer. While initial Hib vaccine responses appeared adequate, the confluence of lower antibody avidity and declining Hib-IgG levels in HEU infants by 12 months support Hib booster vaccination at 1 year. Potential immunologic impairments of HEU infants should be considered in the development of vaccine platforms for populations with high maternal HIV prevalence.Item Kinetics of Nevirapine and Its Impact on HIV-1 RNA Levels in Maternal Plasma and Breast Milk Over Time After Perinatal Single-Dose Nevirapine(JAIDS Journal of Acquired Immune Deficiency Syndromes, 2012) Aizire, Jim; McConnell, Michelle S.; Mudiope, Peter; Mubiru, Michael; Matovu, Flavia; Parsons, Teresa L.; Elbireer, Ali ,; Nolan, Monica; Janoff, Edward N.; Glenn Fowler, MaryTo determine kinetics after single-dose nevirapine and the impact on HIV RNA [viral load (VL)] in maternal plasma and breast milk (BM). Methods: Cohort of 120 HIV-1–infected pregnant Ugandan women received perinatal single-dose nevirapine alone and followed up with their infants through 24 weeks postdelivery. We assessed the relationship of nevirapine concentration (tandem mass spectroscopy) and HIV-1 VL (Roche AMPLICOR HIV-1 Kit, version 1.5) in maternal plasma and BM over time. Results: At week 1 postpartum, NVP ($10 ng/mL) was detected in all 53 plasma and 47 of 51 (92.2%) BM samples with median (inter- quartile ranges) of, respectively, 171 (78–214) ng/mL and 112 (64–158) ng/mL, P = 0.075, which decreased subsequently with traces persisting through week 4 in plasma. Plasma and BM VL dropped by week 1 and were highly correlated at delivery (R = 0.71, P , 0.001) and week 1 (R = 0.69, P , 0.001) but not thereafter. At week 1, VL correlated inversely with NVP concentra- tion in plasma (R = 0.39, P = 0.004) and BM (R = 0.48, P = 0.013). There was a VL rebound in both compartments, which peaked at week 4 to levels greater than those at week 1 [significantly in plasma (P , 0.001) but not in BM] and remained stable thereafter. Median VL was consistently greater (11- to 50-fold) in plasma than BM at all time points (all P , 0.001). Conclusions: After single-dose nevirapine, NVP concentration was comparably high through week 1, accompanied by suppression of plasma and BM VL. A longer “tail” (.1 week) of potent postnatal antiretroviral drugs is warranted to minimize the observed VL rebound and potential for NVP resistance as a result of persistent NVP tracesItem Safety and Efficacy of HIV Hyperimmune Globulin (HIVIGLOB) for Prevention of Mother-to-Child HIV Transmission in HIV-1 infected Pregnant Women and their Infants in Kampala, Uganda (HIVIGLOB/NVP STUDY)(Journal of acquired immune deficiency syndromes, 2011) Makumbi, Carolyne Onyango; Omer, Saad B.; Mubiru, Michael; Moulton, Lawrence H.; Nakabiito, Clemensia; Musoke, Philippa; Mmiro, Francis; Zwerski, Sheryl; Wigzell, Hans; Falksveden, Lars; Wahren, Britta; Antelman, Gretchen; Fowler, Mary Glenn; Guay, Laura; Jackson, J. BrooksThis phase III randomized clinical trial compared single dose nevirapine (sdNVP) plus HIV immunoglobulin (HIVIGLOB) to sdNVP alone for preventing maternal-to-child transmission (PMTCT) of HIV.Primary objectives were to determine rates of HIV infection among infants, and to assess the safety of HIVIGLOB in combination with sdNVP in HIV-infected Ugandan pregnant women and their infants.Mother-infant pairs were randomized to receive 200mg of NVP to women in labor and 2mg/kg NVP to newborns within 72 hours after birth (sdNVP arm) or to receive sdNVP plus a single intravenous 240ml dose of HIVIGLOB given to women at 36-38 weeks gestation and a single intravenous 24ml dose to newborns within 18 hours of birth (HIVIGLOB/sdNVP arm). Risk of HIV infection was determined using Kaplan-Meier and risk ratio estimates at birth, 2, 6, 14 weeks, 6 and 12 months of age. Intent-to-treat analysis included 198 HIVIGLOB/sdNVP and 294 sdNVP mother-infant pairs. At 6 months of age, the primary endpoint, there was no statistically significant difference in HIV transmission in the HIVIGLOB/sdNVP arm versus the sdNVP arm (18.7% vs.15.0%; RR =1.240 [95% CI: 0.833-1.846]; p= 0.290). Similarly, the proportion of serious adverse events in the HIVIGLOB/sdNVP and sdNVP arms, respectively for mothers (18.9% vs. 19.3%; p= 0.91) and infants (62.6% vs. 59.5%; p=0.51), were not significantly different.Giving mother-infant pairs an infusion of peripartum HIV hyperimmunoglobulin in addition to sdNVP for PMTCT was as safe as sdNVP alone, but was no more effective than sdNVP alone in preventing HIV transmission.