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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 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.Item Lessons learnt from the first controlled human malaria infection study conducted in Nairobi, Kenya.(2015-Apr-28) Hodgson, Susanne H.; Juma, Elizabeth; Salim, Amina; Magiri, Charles; Njenga, Daniel; Molyneux, Sassy; Njuguna, Patricia; Awuondo, Ken; Lowe, Brett; Billingsley, Peter F.; Cole, Andrew O.; Ogwang, Caroline; Osier, Faith; Chilengi, Roma; Hoffman, Stephen L.; Draper, Simon J.; Ogutu, Bernhards; Marsh, KevinBACKGROUND: Controlled human malaria infection (CHMI) studies, in which healthy volunteers are infected with Plasmodium falciparum to assess the efficacy of novel malaria vaccines and drugs, have become a vital tool to accelerate vaccine and drug development. CHMI studies provide a cost-effective and expeditious way to circumvent the use of large-scale field efficacy studies to deselect intervention candidates. However, to date few modern CHMI studies have been performed in malaria-endemic countries. METHODS: An open-label, randomized pilot CHMI study was conducted using aseptic, purified, cryopreserved, infectious P. falciparum sporozoites (SPZ) (Sanaria® PfSPZ Challenge) administered intramuscularly (IM) to healthy Kenyan adults (n = 28) with varying degrees of prior exposure to P. falciparum. The purpose of the study was to establish the PfSPZ Challenge CHMI model in a Kenyan setting with the aim of increasing the international capacity for efficacy testing of malaria vaccines and drugs, and allowing earlier assessment of efficacy in a population for which interventions are being developed. This was part of the EDCTP-funded capacity development of the CHMI platform in Africa. DISCUSSION: This paper discusses in detail lessons learnt from conducting the first CHMI study in Kenya. Issues pertinent to the African setting, including community sensitization, consent and recruitment are considered. Detailed reasoning regarding the study design (for example, dose and route of administration of PfSPZ Challenge, criteria for grouping volunteers according to prior exposure to malaria and duration of follow-up post CHMI) are given and changes other centres may want to consider for future studies are suggested. CONCLUSIONS: Performing CHMI studies in an African setting presents unique but surmountable challenges and offers great opportunity for acceleration of malaria vaccine and drug development. The reflections in this paper aim to aid other centres and partners intending to use the CHMI model in Africa.Item The burden of cervical pre-cancer and cancer in HIV positive women in Zambia: a modeling study.(2015-Jul-24) Bateman, Allen C.; Katundu, Katundu; Mwanahamuntu, Mulindi H.; Kapambwe, Sharon; Sahasrabuddhe, Vikrant V.; Hicks, Michael L.; Chi, Benjamin H.; Stringer, Jeffrey S.; Parham, Groesbeck P.; Chibwesha, Carla J.BACKGROUND: HIV infection is associated with a higher incidence of precancerous cervical lesions and their progression to invasive cervical cancer (ICC). Zambia is a global epicenter of HIV and ICC, yet the overall burden of cervical pre-cancer [cervical intraepithelial neoplasia 3 (CIN3)] and ICC among its HIV positive adult female population is unknown. The objective of this study was to determine the burden of cervical disease among HIV positive women in Zambia by estimating the number with CIN3 and ICC. METHODS: We conducted a cross-sectional study among 309 HIV positive women attending screening in Lusaka (Zambia's most populated province) to measure the cervical disease burden by visual inspection with acetic acid enhanced by digital cervicography (DC), cytology, and histology. We then used estimates of the prevalence of CIN3 and ICC from the cross-sectional study and Spectrum model-based estimates for HIV infection among Zambian women to estimate the burden of CIN3 and ICC among HIV positive women nationally. RESULTS: Over half (52 %) of the study participants screened positive by DC, while 45 % had cytologic evidence of high grade squamous intraepithelial lesions (SIL) or worse. Histopathologic evaluation revealed that 20 % of women had evidence of CIN2 or worse, 11 % had CIN3 or worse, and 2 % had ICC. Using the Spectrum model, we therefore estimate that 34,051 HIV positive women in Zambia have CIN3 and 7,297 have ICC. CONCLUSIONS: The DC, cytology, and histology results revealed a large cervical disease burden in this previously unscreened HIV positive population. This very large burden indicates that continued scale-up of cervical cancer screening and treatment is urgently needed.Item Prevalence of hypertension and its treatment among adults presenting to primary health clinics in rural Zambia: analysis of an observational database.(2015-Sep-21) Yan, Lily D.; Chi, Benjamin H.; Sindano, Ntazana; Bosomprah, Samuel; Stringer, Jeffrey S.; Chilengi, RomaBACKGROUND: Hypertension constitutes a growing burden of illness in developing countries like Zambia. Adequately screening and treating hypertension could greatly reduce the complications of stroke and coronary disease. Our objective was to determine the prevalence of hypertension and identify current treatment practices among adult patients presenting for routine care to rural health facilities in the Better Health Outcomes through Mentoring and Assessments (BHOMA) project. METHODS: We conducted a retrospective analysis of routinely collected clinical data from 46 rural government clinics in Zambia. Our analysis cohort comprised patients ≥ 25 years with recorded blood pressure measurements, who sought care at primary health centers. Consistent with prior research, in our primary analysis, we only included data from first visits. Hypertension was defined as a systolic blood pressure ≥140 mmHg, or diastolic blood pressure ≥90 mmHg, or reported use of antihypertensive medication. A sensitivity analysis was performed using median blood pressure for individuals with multiple visits. RESULTS AND DISCUSSION: From January 2011 to December 2014, 116,130 first visits by adult patients met eligibility criteria. The crude prevalence of hypertension by onsite measurement or reported use of antihypertensive medication was 23.1% [95% CI: 22.8-23.3] (23.6% in females, 22.3% in males). The age standardized prevalence of hypertension across participating sites was 28.0 [95% CI: 27.7-28.3] (29.7% in females, 25.8% in males). Sensitivity analysis revealed a similar prevalence using data from all visits. Only 5.6% of patients had a diagnosis of hypertension documented in their medical record. Among patients with hypertension, only 18.0% had any antihypertensive drug prescribed, with nifedipine (8.9%), furosemide (8.3%), and propranolol (2.4%) as the most common. CONCLUSIONS: Age standardized prevalence of hypertension in rural primary health clinics in Zambia was high compared to other studies in rural Africa; however, we diagnosed hypertension with only one measurement and this may have biased our findings. Future efforts to improve hypertension control should focus on population preventive care and primary healthcare provider education on individual management.Item Sustainable HIV treatment in Africa through viral-load-informed differentiated care.(2015-Dec-03) Phillips, Andrew; Shroufi, Amir; Vojnov, Lara; Cohn, Jennifer; Roberts, Teri; Ellman, Tom; Bonner, Kimberly; Rousseau, Christine; Garnett, Geoff; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Bansi-Matharu, Loveleen; Miners, Alec; Lundgren, Jens D.; Eaton, Jeffrey W.; Parkes-Ratanshi, Rosalind; Katz, Zachary; Maman, David; Ford, Nathan; Vitoria, Marco; Doherty, Meg; Dowdy, David; Nichols, Brooke; Murtagh, Maurine; Wareham, Meghan; Palamountain, Kara M.; Chakanyuka, Christine M.; Stevens, Wendy; Katzenstein, David; Ciaranello, Andrea; Barnabas, Ruanne; Braithwaite, Scott R.; Bendavid, Eran; Nathoo, Kusum J.; van de Vijver, David; Wilson, David P.; Holmes, Charles; Bershteyn, Anna; Walker, Simon; Raizes, Elliot; Jani, Ilesh; Nelson, Lisa J.; Peeling, Rosanna; Terris-Prestholt, Fern; Murungu, Joseph; Mutasa-Apollo, Tsitsi ; Hallett, Timothy B.; Revill, PaulThere are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.