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The CIDRZ Research Repository serves as an open-access archive for peer-reviewed publications, conference papers, and other scholarly outputs from CIDRZ researchers. Our goal is to promote the dissemination of knowledge and support evidence-based public health initiatives.
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Item Isolation and characterization of a new simian rotavirus, YK-1.(2006-May-31) Westerman, Larry E.; Jiang, Baoming; McClure, Harold M.; Snipes-Magaldi, Lauren J.; Griffin, Dixie D.; Shin, Gary; Gentsch, Jon R.; Glass, Roger I.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 Use of task-shifting to rapidly scale-up HIV treatment services: experiences from Lusaka, Zambia.(2009-Jan-09) Morris, Mary B.; Tambatamba-Chapula, Bushimbwa; Chi, Benjamin H.; Mwango, Albert; Chi, Harmony F.; Mwanza, Joyce; Manda, Handson; Bolton, Carolyn; Pankratz, Debra S.; Stringer, Jeffrey S.; Reid, Stewart E.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 Burnout and use of HIV services among health care workers in Lusaka District, Zambia: a cross-sectional study.(2009-Jul-13) Kruse, Gina R.; Chapula-Tambatamba, Bushimbwa ; Ikeda, Scott; Nkhoma, Mavis; Quiterio, Nicole; Pankratz, Debra; Mataka, Kaluba; Chi, Benjamin H.; Bond, Virginia; Reid, Stewart E.BACKGROUND: Well-documented shortages of health care workers in sub-Saharan Africa are exacerbated by the increased human resource demands of rapidly expanding HIV care and treatment programmes. The successful continuation of existing programmes is threatened by health care worker burnout and HIV-related illness. METHODS: From March to June 2007, we studied occupational burnout and utilization of HIV services among health providers in the Lusaka public health sector. Providers from 13 public clinics were given a 36-item, self-administered questionnaire and invited for focus group discussions and key-informant interviews. RESULTS: Some 483 active clinical staff completed the questionnaire (84% response rate), 50 staff participated in six focus groups, and four individuals gave interviews. Focus group participants described burnout as feeling overworked, stressed and tired. In the survey, 51% reported occupational burnout. Risk factors were having another job (RR 1.4 95% CI 1.2-1.6) and knowing a co-worker who left in the last year (RR 1.6 95% CI 1.3-2.2). Reasons for co-worker attrition included: better pay (40%), feeling overworked or stressed (21%), moving away (16%), death (8%) and illness (5%). When asked about HIV testing, 370 of 456 (81%) reported having tested; 240 (50%) tested in the last year. In contrast, discussion groups perceived low testing rates. Both discussion groups and survey respondents identified confidentiality as the prime reason for not undergoing HIV testing. CONCLUSION: In Lusaka primary care clinics, overwork, illness and death were common reasons for attrition. Programmes to improve access, acceptability and confidentiality of health care services for clinical providers and to reduce workplace stress could substantially affect workforce stability.Item Selected hematologic and biochemical measurements in African HIV-infected and uninfected pregnant women and their infants: the HIV Prevention Trials Network 024 protocol.(2009-Aug-07) Mwinga, Kasonde; Vermund, Sten H.; Chen, Ying Q.; Mwatha, Anthony; Read, Jennifer S.; Urassa, Willy; Carpenetti, Nicole; Valentine, Megan; Goldenberg, Robert L.BACKGROUND: Reference values for hematological and biochemical assays in pregnant women and in newborn infants are based primarily on Caucasian populations. Normative data are limited for populations in sub-Saharan Africa, especially comparing women with and without HIV infection, and comparing infants with and without HIV infection or HIV exposure. METHODS: We determined HIV status and selected hematological and biochemical measurements in women at 20-24 weeks and at 36 weeks gestation, and in infants at birth and 4-6 weeks of age. All were recruited within a randomized clinical trial of antibiotics to prevent chorioamnionitis-associated mother-to-child transmission of HIV (HPTN024). We report nearly complete laboratory data on 2,292 HIV-infected and 367 HIV-uninfected pregnant African women who were representative of the public clinics from which the women were recruited. Nearly all the HIV-infected mothers received nevirapine prophylaxis at the time of labor, as did their infants after birth (always within 72 hours of birth, but typically within just a few hours at the four study sites in Malawi (2 sites), Tanzania, and Zambia. RESULTS: HIV-infected pregnant women had lower red blood cell counts, hemoglobin, hematocrit, and white blood cell counts than HIV-uninfected women. Platelet and monocyte counts were higher among HIV-infected women at both time points. At the 4-6-week visit, HIV-infected infants had lower hemoglobin, hematocrit and white blood cell counts than uninfected infants. Platelet counts were lower in HIV-infected infants than HIV-uninfected infants, both at birth and at 4-6 weeks of age. At 4-6 weeks, HIV-infected infants had higher alanine aminotransferase measures than uninfected infants. CONCLUSION: Normative data in pregnant African women and their newborn infants are needed to guide the large-scale HIV care and treatment programs being scaled up throughout the continent. These laboratory measures will help interpret clinical data and assist in patient monitoring in a sub-Saharan Africa context.Item Self-reported dietary intake and appetite predict early treatment outcome among low-BMI adults initiating HIV treatment in sub-Saharan Africa.(2013-Mar) Koethe, John R.; Blevins, Meridith; Bosire, Claire; Nyirenda, Christopher; Kabagambe, Edmond K.; Mwango, Albert; Kasongo, Webster; Zulu, Isaac; Shepherd, Bryan E.; Heimburger, Douglas C.OBJECTIVE: Low BMI is a major risk factor for early mortality among HIV-infected persons starting antiretrovial therapy (ART) in sub-Saharan Africa and the common patient belief that antiretroviral medications produce distressing levels of hunger is a barrier to treatment adherence. We assessed relationships between appetite, dietary intake and treatment outcome 12 weeks after ART initiation among HIV-infected adults with advanced malnutrition and immunosuppression. DESIGN: A prospective, observational cohort study. Dietary intake was assessed using a 24 h recall survey. The relationships of appetite, intake and treatment outcome were analysed using time-varying Cox models. SETTING: A public-sector HIV clinic in Lusaka, Zambia. SUBJECTS: One hundred and forty-two HIV-infected adults starting ART with BMI <16 kg/m2 and/or CD4+ lymphocyte count <50 cells/μl. RESULTS: Median age, BMI and CD4+ lymphocyte count were 32 years, 16 kg/m2 and 34 cells/μl, respectively. Twenty-five participants (18%) died before 12 weeks and another thirty-three (23%) were lost to care. A 500 kJ/d higher energy intake at any time after ART initiation was associated with an approximate 16% reduction in the hazard of death (adjusted hazard ratio = 0.84; P = 0.01), but the relative contribution of carbohydrate, protein or fat to total energy was not a significant predictor of outcome. Appetite normalized gradually among survivors and hunger was rarely reported. CONCLUSIONS: Poor early ART outcomes were strikingly high in a cohort of HIV-infected adults with advanced malnutrition and mortality was predicted by lower dietary intake. Intervention trials to promote post-ART intake in this population may benefit survival and are warranted.Item Improving health information systems for decision making across five sub-Saharan African countries: Implementation strategies from the African Health Initiative.(2013) Mutale, Wilbroad; Chintu, Namwinga; Amoroso, Cheryl; Awoonor-Williams, Koku; Phillips, James; Baynes, Colins; Michel, Cathy; Taylor, Angela; Sherr, KennethBACKGROUND: Weak health information systems (HIS) are a critical challenge to reaching the health-related Millennium Development Goals because health systems performance cannot be adequately assessed or monitored where HIS data are incomplete, inaccurate, or untimely. The Population Health Implementation and Training (PHIT) Partnerships were established in five sub-Saharan African countries (Ghana, Mozambique, Rwanda, Tanzania, and Zambia) to catalyze advances in strengthening district health systems. Interventions were tailored to the setting in which activities were planned. COMPARISONS ACROSS STRATEGIES: All five PHIT Partnerships share a common feature in their goal of enhancing HIS and linking data with improved decision-making, specific strategies varied. Mozambique, Ghana, and Tanzania all focus on improving the quality and use of the existing Ministry of Health HIS, while the Zambia and Rwanda partnerships have introduced new information and communication technology systems or tools. All partnerships have adopted a flexible, iterative approach in designing and refining the development of new tools and approaches for HIS enhancement (such as routine data quality audits and automated troubleshooting), as well as improving decision making through timely feedback on health system performance (such as through summary data dashboards or routine data review meetings). The most striking differences between partnership approaches can be found in the level of emphasis of data collection (patient versus health facility), and consequently the level of decision making enhancement (community, facility, district, or provincial leadership). DISCUSSION: Design differences across PHIT Partnerships reflect differing theories of change, particularly regarding what information is needed, who will use the information to affect change, and how this change is expected to manifest. The iterative process of data use to monitor and assess the health system has been heavily communication dependent, with challenges due to poor feedback loops. Implementation to date has highlighted the importance of engaging frontline staff and managers in improving data collection and its use for informing system improvement. Through rigorous process and impact evaluation, the experience of the PHIT teams hope to contribute to the evidence base in the areas of HIS strengthening, linking HIS with decision making, and its impact on measures of health system outputs and impact.Item Estimating the cost-effectiveness of nutrition supplementation for malnourished, HIV-infected adults starting antiretroviral therapy in a resource-constrained setting.(2014) Koethe, John R.; Marseille, Elliot; Giganti, Mark J.; Chi, Benjamin H.; Heimburger, Douglas ; Stringer, Jeffrey S.BACKGROUND: Low body mass index (BMI) individuals starting antiretroviral therapy (ART) for HIV infection in sub-Saharan Africa have high rates of death and loss to follow-up in the first 6 months of treatment. Nutritional supplementation may improve health outcomes in this population, but the anticipated benefit of any intervention should be commensurate with the cost given resource limitations and the need to expand access to ART in the region. METHODS: We used Markov models incorporating historical data and program-wide estimates of treatment costs and health benefits from the Zambian national ART program to estimate the improvements in 6-month survival and program retention among malnourished adults necessary for a combined nutrition support and ART treatment program to maintain cost-effectiveness parity with ART treatment alone. Patients were stratified according to World Health Organization criteria for severe (BMI <16.0 kg/m(2)), moderate (16.00-16.99 kg/m(2)), and mild (17.00-18.49 kg/m(2)) malnutrition categories. RESULTS: 19,247 patients contributed data between May 2004 and October 2010. Quarterly survival and retention were lowest in the BMI <16.0 kg/m(2) category compared to higher BMI levels, and there was less variation in both measures across BMI strata after 180 days. ART treatment was estimated to cost $556 per year and averted 7.3 disability-adjusted life years. To maintain cost-effectiveness parity with ART alone, a supplement needed to cost $10.99 per quarter and confer a 20% reduction in both 6-month mortality and loss to follow-up among BMI <16.0 kg/m(2) patients. Among BMI 17.00-18.49 kg/m(2) patients, supplement costs accompanying a 20% reduction in mortality and loss to follow-up could not exceed $5.18 per quarter. In sensitivity analyses, the maximum permitted supplement cost increased if the ART program cost rose, and fell if patients classified as lost to follow-up at 6 months subsequently returned to care. CONCLUSIONS: Low BMI adults starting ART in sub-Saharan Africa are at high risk of early mortality and loss to follow-up. The expense of providing nutrition supplementation would require only modest improvements in survival and program retention to be cost-effective for the most severely malnourished individuals starting ART, but interventions are unlikely to be cost-effective among those in higher BMI strata.Item Identification of human papillomaviruses from formalin-fixed, paraffin-embedded pre-cancer and invasive cervical cancer specimens in Zambia: a cross-sectional study.(2015-Jan-16) Bateman, Allen C.; Katundu, Katundu; Polepole, Pascal; Shibemba, Aaron; Mwanahamuntu, Mulindi; Dittmer, Dirk P.; Parham, Groesbeck P.; Chibwesha, Carla J.BACKGROUND: The most common human papillomavirus (HPV) genotypes isolated from cervical cancer in select African countries are HPV-16, HPV-18, HPV-35, and HPV-45, but the most common genotypes in Zambia are unknown. The overall objective of this study was to assess the potential impact of current HPV vaccines in preventing cervical cancer in Zambia, by determining the combined prevalence of HPV-16 and/or HPV-18 in invasive cervical cancer (ICC) and high-grade pre-cancer [cervical intraepithelial neoplasia 2 or 3 (CIN2/3)] cases. FINDINGS: We compared DNA extraction techniques to determine which assay performs well in the Zambian context, where unbuffered formalin is used to fix specimens. We then tested specimens with the Abbott RealTime High-Risk HPV test to estimate the prevalence of HPV-16/18 in formalin-fixed, paraffin-embedded ICC and CIN2/3 specimens. DNA extraction using heat (without xylene) was more successful than xylene-based extraction. Over 80% of specimens tested using heat extraction and the Abbott RealTime HPV test were positive for HPV. HPV-16 and/or HPV-18 were identified in 65/93 (69.9%) ICC specimens positive for HPV and in 38/65 (58.5%) CIN2/3 specimens positive for HPV. CONCLUSIONS: To our knowledge this is the first report to identify HPV genotypes in cervical cancers in Zambia. A combined HPV-16/18 prevalence of 69.9% in ICC specimens suggests that current vaccines will be highly protective against cervical cancer in Zambia.Item Identification of viral and bacterial pathogens from hospitalized children with severe acute respiratory illness in Lusaka, Zambia, 2011-2012: a cross-sectional study.(2015-Feb-12) Simusika, Paul; Bateman, Allen C.; Theo, Andros; Kwenda, Geoffrey; Mfula, Christine; Chentulo, Edward; Monze, MwakaBACKGROUND: Morbidity and mortality from respiratory infections are higher in resource-limited countries than developed countries, but limited studies have been conducted in resource-limited settings to examine pathogens from patients with acute respiratory infections. Influenza surveillance has been conducted in Zambia since 2008; however, only 4.3% of patients enrolled in 2011-2012 were positive for influenza. Therefore, we examined non-influenza respiratory pathogens in children with severe acute respiratory illness (SARI) in Zambia, to estimate the scope of disease burden and determine commonly-identified respiratory pathogens. METHODS: Two reverse transcriptase polymerase chain reaction (rRT-PCR) methods (single and multiplex) were used to analyze nasopharyngeal and throat swabs collected from SARI cases under five years of age from January 2011 through December 2012. All specimens were negative for influenza by rRT-PCR. The panel of singleplex reactions targeted seven viruses, while the multiplex assay targeted thirty-three bacteria, fungi, and viruses. RESULTS: A set of 297 specimens were tested by singleplex rRT-PCR, and a different set of 199 were tested by multiplex rRT-PCR. Using the singleplex assay, 184/297 (61.9%) specimens were positive for one or more viruses. The most prevalent viruses were human rhinovirus (57/297; 19.2%), human adenovirus (50/297; 16.8%), and respiratory syncytial virus (RSV) (45/297; 15.2%). Using multiplex PCR, at least one virus was detected from 167/199 (83.9%) specimens, and at least one bacteria was detected from 197/199 (99.0%) specimens. Cytomegalovirus (415/199; 208.5%) and RSV (67/199; 33.7%) were the most commonly detected viruses, while Streptococcus pneumonie (109/199; 54.8%) and Moraxella catarrhalis (92/199; 46.2%) were the most commonly detected bacteria. CONCLUSIONS: Single infections and co-infections of many viruses and bacteria were identified in children with SARI. These results provide an estimate of the prevalence of infection and show which respiratory pathogens are commonly identified in patients. Further studies should investigate causal associations between individual pathogens and SARI.Item The impact of human immunodeficiency virus (HIV) service scale-up on mechanisms of accountability in Zambian primary health centres: a case-based health systems analysis.(2015-Feb-18) Topp, Stephanie M.; Black, Jim; Morrow, Martha; Chipukuma, Julien M.; Van Damme, WimBACKGROUND: Questions about the impact of large donor-funded HIV interventions on low- and middle-income countries' health systems have been the subject of a number of expert commentaries, but comparatively few empirical research studies. Aimed at addressing a particular evidence gap vis-à-vis the influence of HIV service scale-up on micro-level health systems, this article examines the impact of HIV scale-up on mechanisms of accountability in Zambian primary health facilities. METHODS: Guided by the Mechanisms of Effect framework and Brinkerhoff's work on accountability, we conducted an in-depth multi-case study to examine how HIV services influenced mechanisms of administrative and social accountability in four Zambian primary health centres. Sites were selected for established (over 3 yrs) antiretroviral therapy (ART) services and urban, peri-urban and rural characteristics. Case data included provider interviews (60); patient interviews (180); direct observation of facility operations (2 wks/centre) and key informant interviews (14). RESULTS: Resource-intensive investment in HIV services contributed to some early gains in administrative answerability within the four ART departments, helping to establish the material capabilities necessary to deliver and monitor service delivery. Simultaneous investment in external supervision and professional development helped to promote transparency around individual and team performance and also strengthened positive work norms in the ART departments. In the wider health centres, however, mechanisms of administrative accountability remained weak, hindered by poor data collection and under capacitated leadership. Substantive gains in social accountability were also elusive as HIV scale-up did little to address deeply rooted information and power asymmetries in the wider facilities. CONCLUSIONS: Short terms gains in primary-level service accountability may arise from investment in health system hardware. However, sustained improvements in service quality and responsiveness arising from genuine improvements in social and administrative accountability require greater understanding of, and investment in changing, the power relations, work norms, leadership and disciplinary mechanisms that shape these micro-level health systems.