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Permanent URI for this collectionhttps://pubs.cidrz.org/handle/123456789/10189
Welcome to the CIDRZ Published Research Collection. This collection serves as a central repository of peer-reviewed publications authored, co-authored, or supported by the Centre for Infectious Disease Research in Zambia (CIDRZ). It provides open access to scientific knowledge that contributes to public health, clinical research, and evidence-based policy in Zambia and beyond.
Browse the collection to explore research covering HIV, TB, maternal and child health, health systems strengthening, and other key public health topics. Articles are frequently harvested from PubMed and other trusted databases.
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Item Effectiveness of a city-wide program to prevent mother-to-child HIV transmission in Lusaka, Zambia.(2005-Aug-12) Stringer JS; Sinkala M; Maclean CC; Levy J; Kankasa C; Degroot A; Stringer EM; Acosta EP; Goldenberg RL; Vermund SH; Schools of Medicine and Public Health, University of Alabama at Birmingham, USA. stringer@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)OBJECTIVE: To determine the population effectiveness of a city-wide perinatal HIV prevention program. DESIGN: An anonymous surveillance of newborn cord blood for HIV serology and nevirapine (NVP). METHODS: All 10 public-sector delivery centers in Lusaka, Zambia participated. All mother-infant pairs delivering during the 12-week surveillance period at the participating centers and who received antenatal care at a public-sector facility in Lusaka were included in the study. The main outcome measure was population NVP coverage, defined as the proportion of HIV-infected women and HIV-exposed infants in the population that ingested NVP. RESULTS: Of 8787 women in the surveillance population, 7204 (82%) had been offered antenatal HIV testing, of which 5149 (71%) had accepted, and of which 5129 (99%) had received a result. Overall, 2257 of 8787 (26%) were cord seropositive. Of the 1246 (55%) cord blood seropositive women who received an antenatal HIV test result, 1112 (89%) received a positive result; the other 134 comprise seroconverters and clerical errors. Only 751 of 1112 (68%) women who received a positive antenatal test result and a NVP tablet for ingestion at labor onset had NVP detected in the cord blood (i.e., maternal non-adherence rate was 32%). A total of 675 infants born to 751 adherent mothers (90%) received NVP before discharge. Thus, only 675 of 2257 (30%) seropositive mother-infant pairs in the surveillance population received both a maternal and infant dose of NVP. CONCLUSIONS: Successful perinatal HIV prevention requires each mother-infant pair to negotiate a cascade of events that begins with offering HIV testing and continues through adherence to the prescribed regimen. This novel surveillance demonstrates that failures occur at each step, resulting in reduced coverage and diminished program effectiveness.Item Timing of maternal and neonatal dosing of nevirapine and the risk of mother-to-child transmission of HIV-1: HIVNET 024.(2005-Nov-04) Chi BH; Wang L; Read JS; Sheriff M; Fiscus S; Brown ER; Taha TE; Valentine M; Goldenberg R; University of Alabama at Birmingham, Department of Obstetrics & Gynecology, Birmingham, Alabama, USA. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)OBJECTIVE: Despite a growing emphasis worldwide on complex and potent antiretroviral drug regimens for the prevention of mother-to-child transmission of HIV-1 (MTCT), two-dose nevirapine (NVP) prophylaxis remains an important choice in many settings. We analyzed data from a multicenter clinical trial to determine whether timing of maternal or infant NVP was associated with MTCT between delivery and 6 weeks of age (intrapartum/early postnatal transmission; I/EP). METHODS: HIVNET 024 was a placebo-controlled, double-blind trial of empiric antibiotics to reduce chorioamnionitis-associated MTCT. This secondary analysis used data collected in the original randomized trial. Enrolled women were instructed to self-administer NVP at labor onset; infants were to receive a dose within 72 h of birth. RESULTS: Data regarding 1491 mother-infant pairs were analyzed. The overall I/EP HIV-1 transmission rate was 8.1% at 6 weeks. Almost all women (93%) ingested NVP within 24 h of delivery; 90% of infants were given NVP within 48 h after delivery. Variations in mother or infant dose timing did not influence transmission rates, even when the combined pattern of both was taken into account through multivariate analysis. In the subset of women ingesting NVP or= 4 h). CONCLUSION: Variations in the timing of maternal and infant NVP doses (within reasonable proximity to delivery) do not appear to affect the risk of MTCT.Item Cost and enrollment implications of targeting different source population for an HIV treatment program.(2005-Nov-01) Chi BH; Fusco H; Sinkala M; Goldenberg RL; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Rapid scale-up of antiretroviral therapy (ART) is a worldwide priority, and ambitious targets for numbers on ART have been set. Antenatal clinics (ANCs) and tuberculosis (TB) clinics have been targeted as entry points into HIV care. METHODS: We developed a conditional probability model to evaluate the effects of ANC and TB clinic populations on ART program enrollment. RESULTS: To start 1 individual on ART, 3 TB patients have to be screened at a crude program cost of 36 US dollars per patient initiated on therapy. By contrast, 48 ANC patients have to be screened at a cost of US 214 US dollars per patient on therapy. In an incremental analysis in which ANC HIV testing was borne by a program to prevent mother-to-child transmission, recruitment efficiency increased (8 screened per patient starting ART) and cost decreased (114 US dollars per patient on therapy). Absolute numbers starting ART, however, remained fixed. If all 60,000 ANC patients seen yearly in the Lusaka District were screened, 1247 would start ART. Approaching the district's 35,000 annual TB patients would generate 11,947 patients on ART. CONCLUSION: In areas with high HIV prevalence, targeting chronically ill populations for HIV treatment may have significant short-term benefits in cost savings and recruitment efficiency.Item Isolation and characterization of a new simian rotavirus, YK-1.(2006-May-31) Westerman LE; Jiang B; McClure HM; Snipes-Magaldi LJ; Griffin DD; Shin G; Gentsch JR; Glass RI; Viral Gastroenteritis Team, Respiratory and Enteric Viruses Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. larry@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: To effectively analyze the requirements for protection to rotavirus infection, a reliable animal model that reasonably mimics infection and disease in humans is needed. A requirement for an effective animal model is the availability of appropriate rotavirus stocks for challenge. RESULTS: A new simian rotavirus, designated YK-1, was isolated from a 2-year-old immunodeficient pigtailed macaque with chronic diarrhea. YK-1 was distinguishable by electropherotype from the other simian rotavirus strains, SA11 and RRV. One variant of YK-1, clone 311, which was isolated after adaptation and plaque purification in cell cultures, displayed an unusual RNA electropherotype with an abnormally migrating gene 11 segment. Sequence analysis demonstrated a genetic rearrangement that involved a partial duplication of the gene 11 ORF encoding NSP5. YK-1 was identified as a Group A rotavirus belonging to subgroup 1. To further characterize the YK-1 strain, the genes encoding VP4, VP7, and NSP4 were sequenced. Analysis of VP4 and VP7 gene fragments suggests that this strain is a G3P3 rotavirus and is closely related to the simian rotavirus strain RRV. Serotype analysis also identified YK-1 as a G3 rotavirus. The NSP4 genotype of YK-1 is C, the same genotype as RRV. CONCLUSION: This newly isolated rotavirus, YK-1, is being used to establish a nonhuman primate model for studying the infectivity, immunity, and pathogenesis of rotavirus and for evaluating candidate rotavirus vaccines.Item Early clinical and immune response to NNRTI-based antiretroviral therapy among women with prior exposure to single-dose nevirapine.(2007-May-11) Chi BH; Sinkala M; Stringer EM; Cantrell RA; Mtonga V; Bulterys M; Zulu I; Kankasa C; Wilfert C; Weidle PJ; Vermund SH; Stringer JS; Centre for Infectious Disease Research in Zambia, Zambia. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)OBJECTIVE: To determine whether prior exposure to single-dose nevirapine (NVP) for prevention of mother-to-child HIV transmission (PMTCT) is associated with attenuated CD4 cell response, death, or clinical treatment failure in women starting antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTI). METHODS: Open cohort evaluation of outcomes for women in program sites across Zambia. HIV treatment was provided according to Zambian/World Health Organization guidelines. RESULTS: Peripartum NVP exposure status was known for 6740 women initiating NNRTI-containing ART, of whom 751 (11%) reported prior use of NVP for PMTCT. There was no significant difference in mean CD4 cell change between those exposed or unexposed to NVP at 6 (+202 versus +182 cells/microl; P = 0.20) or 12 (+201 versus +211 cells/microl; P = 0.60) months. Multivariable analyses showed no significant differences in mortality [adjusted hazard ratio (HR), 1.2; 95% confidence interval (CI), 0.8-1.8] or clinical treatment failure (adjusted HR, 1.1; 95% CI, 0.8-1.5). Comparison of recent NVP exposure with remote exposure suggested a less favorable CD4 cell response at 6 (+150 versus +219 cells/microl; P = 0.06) and 12 (+149 versus +215 cells/microl; P = 0.39) months. Women with recent NVP exposure also had a trend towards elevated risk for clinical treatment failure (adjusted HR, 1.6; 95% CI, 0.9-2.7). CONCLUSION: Exposure to maternal single-dose NVP was not associated with substantially different short-term treatment outcomes. However, evidence was suggestive that exposure within 6 months of ART initiation may be a risk factor for poor treatment outcomes, highlighting the importance of ART screening and initiation early in pregnancy.Item Do targeted HIV programs improve overall care for pregnant women?: Antenatal syphilis management in Zambia before and after implementation of prevention of mother-to-child HIV transmission programs.(2008-Jan-01) Potter D; Goldenberg RL; Chao A; Sinkala M; Degroot A; Stringer JS; Bulterys M; Vermund SH; Schools of Public Health and Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. dara.potter@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: The implementation of disease-specific research or service programs may have an ancillary beneficial or harmful impact on routine clinical services. METHODS: We reviewed the records of 5801 first visits to 22 antenatal clinics from 1997 to 2004 in Lusaka, Zambia and examined documented syphilis rapid plasma reagin (RPR) screening and syphilis treatment before and after implementation of research and/or service programs in prevention of mother-to-child (PMTCT) HIV transmission. FINDINGS: Compared with before PMTCT program implementation, the prevalence odds ratios (PORs) and 95% confidence intervals (CIs) for documented RPR screening were 0.9 (0.7 to 1.1) after implementation of research, 0.7 (0.6 to 0.8) after service, and 2.5 (2.1 to 3.0) after research and service programs. CONCLUSIONS: Documented RPR screening was improved after implementation of PMTCT research and service were operating simultaneously and not with research or service alone. Health policy makers and researchers should plan explicitly for how the targeted HIV programs, service, and/or research can have a broader primary care impact.Item Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission.(2008-Jun-01) Chi BH; Chintu N; Cantrell RA; Kankasa C; Kruse G; Mbewe F; Sinkala M; Smith PJ; Stringer EM; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)OBJECTIVE: To determine the impact of adjuvant single-dose peripartum tenofovir/emtricitabine (TDF/FTC) on intrapartum/early postpartum HIV transmission. METHODS: In the setting of routine short-course zidovudine (ZDV) and peripartum nevirapine (NVP) for perinatal HIV prevention, participants were randomized to single-dose TDF (300 mg)/FTC (200 mg) or to no intervention in labor. Six-week infant HIV infection was compared according to actual-use drug regimens. RESULTS: Of 397 women randomized, 355 (89%) had infants who were alive and active at 6 weeks postpartum. Of these, 18 (5.1%) were infected in utero and 6 (1.8%) were infected intrapartum/early postpartum. Among the 243 who used ZDV and NVP, intrapartum/early postpartum transmission was not reduced among infants whose mothers received TDF/FTC compared with those who did not (2 of 123 [1.6%] vs. 3 of 109 [2.8%]; P = 0.67). Among the 49 infants whose mothers did not receive antenatal ZDV but who had confirmed NVP ingestion, transmission similarly did not differ (0 of 19 [0%] vs. 1 of 26 [3.4%]). TDF/FTC was not significantly associated with reduced overall transmission (odds ratio [OR] = 0.7, 95% confidence interval [CI]: 0.3 to 1.6), even when other antiretroviral drugs were considered (adjusted OR = 0.8, 95% CI: 0.3 to 1.8). CONCLUSIONS: Adjuvant peripartum single-dose TDF/FTC did not reduce perinatal transmission. Whether a higher dose might be effective remains unknown but should be studied in settings in which NVP is used without antenatal ZDV.Item A pilot study of food supplementation to improve adherence to antiretroviral therapy among food-insecure adults in Lusaka, Zambia.(2008-Oct-01) Cantrell RA; Sinkala M; Megazinni K; Lawson-Marriott S; Washington S; Chi BH; Tambatamba-Chapula B; Levy J; Stringer EM; Mulenga L; Stringer JS; Centre for Infectious Disease Research in Zambia, Plot 1275 Lubutu Road, Lusaka, Zambia. cantrell@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: The provision of food supplementation to food-insecure patients initiating antiretroviral therapy (ART) may improve adherence to medications. METHODS: A home-based adherence support program at 8 government clinics assessed patients for food insecurity. Four clinics provided food supplementation, and 4 acted as controls. The analysis compared adherence (assessed by medication possession ratio), CD4, and weight gain outcomes among food-insecure patients enrolled at the food clinics with those enrolled at the control clinics. RESULTS: Between May 1, 2004, and March 31, 2005, 636 food- insecure adults were enrolled. Food supplementation was associated with better adherence to therapy. Two hundred fifty-eight of 366 (70%) patients in the food group achieved a medication possession ratio of 95% or greater versus 79 of 166 (48%) among controls (relative risk = 1.5; 95% confidence interval: 1.2 to 1.8). This finding was unchanged after adjustment for sex, age, baseline CD4 count, baseline World Health Organization stage, and baseline hemoglobin. We did not observe a significant effect of food supplementation on weight gain or CD4 cell response. CONCLUSIONS: This analysis suggests that providing food to food-insecure patients initiating ART is feasible and may improve adherence to medication. A large randomized study of the clinical benefits of food supplementation to ART patients is urgently needed to inform international policy.Item Use of task-shifting to rapidly scale-up HIV treatment services: experiences from Lusaka, Zambia.(2009-Jan-09) Morris MB; Chapula BT; Chi BH; Mwango A; Chi HF; Mwanza J; Manda H; Bolton C; Pankratz DS; Stringer JS; Reid SE; Centre for Infectious Disease Research in Zambia; Lusaka, Zambia. mary.morris@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)The World Health Organization advocates task-shifting, the process of delegating clinical care functions from more specialized to less specialized health workers, as a strategy to achieve the United Nations Millennium Development Goals. However, there is a dearth of literature describing task shifting in sub-Saharan Africa, where services for antiretroviral therapy (ART) have scaled up rapidly in the face of generalized human resource crises. As part of ART services expansion in Lusaka, Zambia, we implemented a comprehensive task-shifting program among existing health providers and community-based workers. Training begins with didactic sessions targeting specialized skill sets. This is followed by an intensive period of practical mentorship, where providers are paired with trainers before working independently. We provide on-going quality assessment using key indicators of clinical care quality at each site. Program performance is reviewed with clinic-based staff quarterly. When problems are identified, clinic staff members design and implement specific interventions to address targeted areas. From 2005 to 2007, we trained 516 health providers in adult HIV treatment; 270 in pediatric HIV treatment; 341 in adherence counseling; 91 in a specialty nurse "triage" course, and 93 in an intensive clinical mentorship program. On-going quality assessment demonstrated improvement across clinical care quality indicators, despite rapidly growing patient volumes. Our task-shifting strategy was designed to address current health care worker needs and to sustain ART scale-up activities. While this approach has been successful, long-term solutions to the human resource crisis are also urgently needed to expand the number of providers and to slow staff migration out of the region.Item HIV incidence rates and risk factors for urban women in Zambia: preparing for a microbicide clinical trial.(2009-Mar) Kapina M; Reid C; Roman K; Cyrus-Cameron E; Kwiecien A; Weiss S; Vermund SH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)OBJECTIVES: A preparedness study was conducted to evaluate the suitability of sites and populations following the same study procedures intended for a larger scale microbicide efficacy trial. In the process the study evaluated human immunodeficiency virus (HIV) incidence, prevalence, and risk profiles for HIV-acquisition among young women in urban Zambia. METHODS: Women aged 16 to 49 years were screened for participation in the study that involved HIV/sexually transmitted infection testing and the assessment of sexual behavioral characteristics. Two hundred thirty-nine eligible women were enrolled and followed up for 12 months. RESULTS: Baseline HIV prevalence at screening was 38.7% (95% CI: 34.2%-43.3%). The highest age-specific prevalence of HIV was 54.1% (95% CI: 46.3%-61.8%) seen in women aged 26 to 34 years. HIV incidence was 2.6% per 100 woman years. Pregnancy rates were high at 17.4 per 100 woman years (95% CI: 12.2-24.1). CONCLUSION: It was concluded that our general population sample, characterized by high HIV prevalence and ongoing incidence rates despite receiving regular risk reduction counseling and free condoms qualifies for future microbicide studies.A microbicide preparedness study conducted in Lusaka, Zambia found high HIV prevalence and appreciable HIV incidence in a population of women in an urban setting.