Browsing by Author "Chintu N"

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A mobile phone-based, community health worker program for referral, follow-up, and service outreach in rural Zambia: outcomes and overview.
(2014-Aug) Schuttner L; Sindano N; Theis M; Zue C; Joseph J; Chilengi R; Chi BH; Stringer JS; Chintu N; 1 Centre for Infectious Disease Research in Zambia , Lusaka, Zambia .; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Mobile health (m-health) utilizes widespread access to mobile phone technologies to expand health services. Community health workers (CHWs) provide first-level contact with health facilities; combining CHW efforts with m-health may be an avenue for improving primary care services. As part of a primary care improvement project, a pilot CHW program was developed using a mobile phone-based application for outreach, referral, and follow-up between the clinic and community in rural Zambia. MATERIALS AND METHODS: The program was implemented at six primary care sites. Computers were installed at clinics for data entry, and data were transmitted to central servers. In the field, using a mobile phone to send data and receive follow-up requests, CHWs conducted household health surveillance visits, referred individuals to clinic, and followed up clinic patients. RESULTS: From January to April 2011, 24 CHWs surveyed 6,197 households with 33,304 inhabitants. Of 15,539 clinic visits, 1,173 (8%) had a follow-up visit indicated and transmitted via a mobile phone to designated CHWs. CHWs performed one or more follow-ups on 74% (n=871) of active requests and obtained outcomes on 63% (n=741). From all community visits combined, CHWs referred 840 individuals to a clinic. CONCLUSIONS: CHWs completed all planned aspects of surveillance and outreach, demonstrating feasibility. Components of this pilot project may aid clinical care in rural settings and have potential for epidemiologic and health system applications. Thus, m-health has the potential to improve service outreach, guide activities, and facilitate data collection in Zambia.
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.
Associations between health systems capacity and mother-to-child HIV prevention program outcomes in Zambia.
(2018) Price JT; Chi BH; Phiri WM; Ayles H; Chintu N; Chilengi R; Stringer JSA; Mutale W; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Society for Family Health, Lusaka, Zambia.; University of Zambia School of Public Health, Lusaka, Zambia.; School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.; UNC Global Projects Zambia, Lusaka, Zambia.; Zambart, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: Zambia has made substantial investments in health systems capacity, yet it remains unclear whether improved service quality improves outcomes. We investigated the association between health system capacity and use of prevention of mother-to-child HIV transmission (PMTCT) services in Zambia. MATERIALS AND METHODS: We analyzed data from two studies conducted in rural and semi-urban Lusaka Province in 2014-2015. Health system capacity, our primary exposure, was measured with a validated balanced scorecard approach. Based on WHO building blocks for health systems strengthening, we derived overall and domain-specific facility scores (range: 0-100), with higher scores indicating greater capacity. Our outcome, community-level maternal antiretroviral drug use at 12 months postpartum, was measured via self-report in a large cohort study evaluating PMTCT program impact. Associations between health systems capacity and our outcome were analyzed via linear regression. RESULTS: Among 29 facilities, median overall facility score was 72 (IQR:67-74). Median domain scores were: patient satisfaction 75 (IQR 71-78); human resources 85 (IQR:63-87); finance 50 (IQR:50-67); governance 82 (IQR:74-91); service capacity 77 (IQR:68-79); service provision 60 (IQR:52-76). Our programmatic outcome was measured from 804 HIV-infected mothers. Median community-level antiretroviral use at 12 months was 81% (IQR:69-89%). Patient satisfaction was the only domain score significantly associated with 12-month maternal antiretroviral use (β:0.22; p = 0.02). When we excluded the human resources and finance domains, we found a positive association between composite 4-domain facility score and 12-month maternal antiretroviral use in peri-urban but not rural facilities. CONCLUSIONS: In these Zambian health facilities, patient satisfaction was positively associated with maternal antiretroviral 12 months postpartum. The association between overall health system capacity and maternal antiretroviral drug use was stronger in peri-urban versus rural facilities. Additional work is needed to guide strategic investments for improved outcomes in HIV and broader maternal-child health region-wide.
Causes of morbidity among HIV-infected children on antiretroviral therapy in primary care facilities in Lusaka, Zambia.
(2009-Oct) Mubiana-Mbewe M; Bolton-Moore C; Banda Y; Chintu N; Nalubamba-Phiri M; Giganti M; Guffey MB; Sambo P; Stringer EM; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: To describe the pattern of incident illness in children after initiation of antiretroviral therapy (ART) in a large public health sector programme in Lusaka, Zambia. METHODS: Systematic chart review to retrospectively extract data from medical records of children (i.e. <15 years) initiating ART in the Lusaka, Zambia public sector. Incident conditions were listed separately and then grouped according to broad categories. Predictors for incident diagnoses were determined using univariate and multivariable analysis. RESULTS: Between May 2004 and June 2006, 1705 HIV-infected children initiated ART. Of these, 1235 (72%) had their medical records reviewed. Median age at ART initiation was 77 months and 554 (45%) were females. Eight hundred and forty-one (68%) children had an incident condition during this period, with a median time of occurrence of 64 days from ART initiation. Twenty-eight incident conditions were documented. When categorized, the most common were mucocutaneous conditions [incidence rate (IR): 70.6 per 100 child-years, 95% CI: 64.5-77.2] and upper respiratory tract infection (IR: 70.1 per 100 child-years; 95% CI: 64.0-76.7). Children with severe immunosuppression (i.e. CD4 < 10%) were more likely to develop lower respiratory tract infection (16.3%vs. 10.2%; P = 0.003) and mucocutaneous conditions (43.9% vs. 35.3%; P = 0.005) than those with CD4 > or = 10%. CONCLUSION: There is a high incidence of new illness after ART initiation, emphasizing the importance of close monitoring during this period. Early initiation of ART and use of antimicrobial prophylaxis may also help to reduce the occurrence of such co-morbidities.
Causes of stillbirth, neonatal death and early childhood death in rural Zambia by verbal autopsy assessments.
(2011-Jul) Turnbull E; Lembalemba MK; Guffey MB; Bolton-Moore C; Mubiana-Mbewe M; Chintu N; Giganti MJ; Nalubamba-Phiri M; Stringer EM; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: To describe specific causes of the high rates of stillbirth, neonatal death and early child childhood death in Zambia. METHODS: We conducted a household-based survey in rural Zambia. Socio-demographic and delivery characteristics were recorded, alongside a maternal HIV test. Verbal autopsy questionnaires were administered to elicit mortality-related information and independently reviewed by three experienced paediatricians who assigned a cause and contributing factor to death. For this secondary analysis, deaths were categorized into: stillbirths (foetal death ≥28 weeks of gestation), neonatal deaths (≤28 days) and early childhood deaths (>28 days to <2 years). RESULTS: Among 1679 households, information was collected on 148 deaths: 34% stillbirths, 26% neonatal and 40% early childhood deaths. Leading identifiable causes of stillbirth were intrauterine infection (26%) and birth asphyxia (18%). Of 32 neonatal deaths, 38 (84%) occurred within the first week of life, primarily because of infections (37%) and prematurity (34%). The majority of early childhood deaths were caused by suspected bacterial infections (82%). HIV prevalence was significantly higher in mothers who reported an early childhood death (44%) than mothers who did not (17%; P < 0.01). Factors significantly associated with mortality were lower socio-economic status (P < 0.01), inadequate water or sanitation facilities (P < 0.01), home delivery (P = 0.04) and absence of a trained delivery attendant (P < 0.01). CONCLUSION: We provide community-level data about the causes of death among children under 2 years of age. Infectious etiologies for mortality ranked highest. At a public health level, such information may have an important role in guiding prevention and treatment strategies to address perinatal and early childhood mortality.
Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia.
(2007-Oct-24) 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; Centre for Infectious Disease Research in Zambia, Lusaka.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Coverage of nevirapine-based services to prevent mother-to-child HIV transmission in 4 African countries.
(2010-Jul-21) Stringer EM; Ekouevi DK; Coetzee D; Tih PM; Creek TL; Stinson K; Giganti MJ; Welty TK; Chintu N; Chi BH; Wilfert CM; Shaffer N; Dabis F; Stringer JS; Centre for Infectious Disease Research in Zambia, Plot 1275 Lubutu Rd, PO Box 34681, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
CONTEXT: Few studies have objectively evaluated the coverage of services to prevent transmission of human immunodeficiency virus (HIV) from mother to child. OBJECTIVE: To measure the coverage of services to prevent mother-to-child HIV transmission in 4 African countries. DESIGN, SETTING, AND PATIENTS: Cross-sectional surveillance study of mother-infant pairs using umbilical cord blood samples collected between June 10, 2007, and October 30, 2008, from 43 randomly selected facilities (grouped as 25 service clusters) providing delivery services in Cameroon, Côte d'Ivoire, South Africa, and Zambia. All sites used at least single-dose nevirapine to prevent mother-to-child HIV transmission and some sites used additional prophylaxis drugs. MAIN OUTCOME MEASURE: Population nevirapine coverage, defined as the proportion of HIV-exposed infants in the sample with both maternal nevirapine ingestion (confirmed by cord blood chromatography) and infant nevirapine ingestion (confirmed by direct observation). RESULTS: A total of 27,893 cord blood specimens were tested, of which 3324 were HIV seropositive (12%). Complete data for cord blood nevirapine results were available on 3196 HIV-seropositive mother-infant pairs. Nevirapine coverage varied significantly by site (range: 0%-82%). Adjusted for country, the overall coverage estimate was 51% (95% confidence interval [CI], 49%-53%). In multivariable analysis, failed coverage of nevirapine-based services was significantly associated with maternal age younger than 20 years (adjusted odds ratio [AOR], 1.44; 95% CI, 1.18-1.76) and maternal age between 20 and 25 years (AOR, 1.28; 95% CI, 1.07-1.54) vs maternal age of older than 30 years; 1 or fewer antenatal care visits (AOR, 2.91; 95% CI, 2.40-3.54), 2 or 3 antenatal care visits (AOR, 1.93; 95% CI, 1.60-2.33), and 4 or 5 antenatal care visits (AOR, 1.56; 95% CI, 1.34-1.80) vs 6 or more antenatal care visits; vaginal delivery (AOR, 1.22; 95% CI, 1.03-1.44) vs cesarean delivery; and infant birth weight of less than 2500 g (AOR, 1.34; 95% CI, 1.11-1.62) vs birth weight of 3500 g or greater. CONCLUSION: In this random sampling of sites with services to prevent mother-to-child HIV transmission, only 51% of HIV-exposed infants received the minimal regimen of single-dose nevirapine.
Determinants of stillbirth in Zambia.
(2011-May) Stringer EM; Vwalika B; Killam WP; Giganti MJ; Mbewe R; Chi BH; Chintu N; Rouse D; Goldenberg RL; Stringer JSA; From the University of Alabama at Birmingham School of Medicine, Birmingham, Alabama; the Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; the University Teaching Hospital, Ministry of Health Zambia, Lusaka, Zambia; the Ministry of Health Zambia, Ndeke House, Lusaka, Zambia; Brown University, Providence, Rhode Island; and Drexel University, Philadelphia, Pennsylvania.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: The objective of this study was to estimate the rates and determinants of stillbirth in an urban African obstetric population. METHODS: In this retrospective cohort study, we reviewed vital outcomes of newborns whose mothers received antenatal care, delivery care, or both antenatal and delivery care in the Lusaka, Zambia, public sector between February 2006 and March 2009. We excluded newborns weighing less than 1,000 g, those whose mothers died before delivery, and those born outside Lusaka. RESULTS: There were 100,454 deliveries that met criteria for inclusion. The median maternal age at the initial visit was 24 years (interquartile range 21-29) and the median gestational age was 22 weeks (interquartile range 19-26). The median gestational age at birth was 38 weeks (interquartile range 36-40), and the median neonatal birth weight was 3,000 g (interquartile range 2,750-3,300). A total of 2,109 fetuses were stillborn (crude rate, 21 per 1,000 live births, 95% confidence interval 20.1 per 1,000 to 21.9 per 1,000). This included 1,049 (49.7%) stillbirths classified as "recent" (presumed to have occurred within 12 hours of delivery) and 1,060 (50.3%) classified as "macerated" (presumed to have occurred more than 12 hours before delivery). In adjusted analysis, increasing maternal age, baseline body mass index greater than 26, history of stillbirth, placental abruption, maternal untreated syphilis, cesarean delivery, operative vaginal delivery, assisted breech delivery, and extremes of neonatal birth weight were all significantly associated with stillbirth. CONCLUSION: Stillbirth is a major contributor to poor perinatal outcomes in Lusaka. Many deaths appear avoidable through investment in antenatal screening and better labor monitoring. Stillbirth should be adopted as a routine health indicator by the World Health Organization.
Early clinical and programmatic outcomes with tenofovir-based antiretroviral therapy in Zambia.
(2010-May-01) Chi BH; Mwango A; Giganti M; Mulenga LB; Tambatamba-Chapula B; Reid SE; Bolton-Moore C; Chintu N; Mulenga PL; Stringer EM; Sheneberger R; Mwaba P; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: In July 2007, amid some controversy over cost, Zambia was the first African country to introduce tenofovir (TDF) as a component of first-line antiretroviral therapy (ART) on a wide scale. METHODS: We compared drug substitutions, mortality, and "programmatic failure" among adults starting TDF-, zidovudine (ZDV)-, and stavudine (d4T)-containing ART. Programmatic failure was defined as death, withdrawal, or loss to follow-up. RESULTS: Between July 2007 and January 2009, 10,485 adults initiated ART (66% on TDF, 23% on ZDV, 11% on d4T), with a median follow-up time of 239 (interquartile range 98, 385) days. Those starting TDF were more likely to be male and more likely to have indicators of severe disease at baseline. In adjusted Cox proportional hazards models, ZDV- (adjusted hazard ratio [AHR] = 2.74, 95% confidence interval [CI] = 2.30-3.28) and d4T-based regimens (AHR = 1.92, 95% CI = 1.55-2.38) were associated with higher risk for drug substitution when compared with TDF-based regimens. Similar hazards were noted for overall mortality (ZDV: AHR = 0 .81, 95% CI = 0.62-1.06; d4T: AHR = 1.03, 95% CI = 0.74-1.43) and programmatic failure (ZDV: AHR = 0.99, 95% CI = 0.88-1.11; d4T: AHR = 1.11, 95% CI = 0.96-1.28) when compared with TDF. CONCLUSIONS: TDF is associated with similar clinical and programmatic outcomes as ZDV and d4T but appears to be better tolerated. Although further evaluation is needed, these results are encouraging and support Zambia's policy decision.
Implementation and Operational Research: Distance From Household to Clinic and Its Association With the Uptake of Prevention of Mother-to-Child HIV Transmission Regimens in Rural Zambia.
(2015-Nov-01) Escamilla V; Chibwesha CJ; Gartland M; Chintu N; Mubiana-Mbewe M; Musokotwane K; Musonda P; Miller WC; Stringer JS; Chi BH; *Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL; †Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; ‡Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC; §Institute for Global Health, Vanderbilt University, Nashville, TN; ‖Society for Family Health, Lusaka, Zambia; ¶Zambian Ministry of Community Development and Mother-Child Health, Lusaka, Zambia; #Department of Public Health, University of Zambia School of Medicine, Lusaka, Zambia; **Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC; ††Department of Epidemiology, Gillings School of Public Health, University of North Carolina, Chapel Hill, NC; and ‡‡Currently at Departments of Medicine and Pediatrics, Massachusetts General Hospital; Boston, MA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: In rural settings, HIV-infected pregnant women often live significant distances from facilities that provide prevention of mother-to-child transmission (PMTCT) services. METHODS: We offered universal maternal combination antiretroviral regimens in 4 pilot sites in rural Zambia. To evaluate the impact of services, we conducted a household survey in communities surrounding each facility. We collected information about HIV status and antenatal service utilization from women who delivered in the past 2 years. Using household Global Positioning System coordinates collected in the survey, we measured Euclidean (i.e., straight line) distance between individual households and clinics. Multivariable logistic regression and predicted probabilities were used to determine associations between distance and uptake of PMTCT regimens. RESULTS: From March to December 2011, 390 HIV-infected mothers were surveyed across four communities. Of these, 254 (65%) had household geographical coordinates documented. One hundred sixty-eight women reported use of a PMTCT regimen during pregnancy including 102 who initiated a combination antiretroviral regimen. The probability of PMTCT regimen initiation was the highest within 1.9 km of the facility and gradually declined. Overall, 103 of 145 (71%) who lived within 1.9 km of the facility initiated PMTCT versus 65 of 109 (60%) who lived farther away. For every kilometer increase, the association with PMTCT regimen uptake (adjusted odds ratio: 0.90, 95% confidence interval: 0.82 to 0.99) and combination antiretroviral regimen uptake (adjusted odds ratio: 0.88, 95% confidence interval: 0.80 to 0.97) decreased. CONCLUSIONS: In this rural African setting, uptake of PMTCT regimens was influenced by distance to health facility. Program models that further decentralize care into remote communities are urgently needed.
Improving health information systems for decision making across five sub-Saharan African countries: Implementation strategies from the African Health Initiative.
(2013) Mutale W; Chintu N; Amoroso C; Awoonor-Williams K; Phillips J; Baynes C; Michel C; Taylor A; Sherr K; Centre for Infectious Disease Research in Zambia, Zambia. wmutale@yahoo.com; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: 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.
Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention.
(2009-Nov) Chi BH; Ellis GM; Chintu N; Cantrell RA; Sinkala M; Aldrovandi GM; Warrier R; Mbewe F; Nakamura K; Stringer EM; Frenkel LM; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
A single dose of tenofovir/emtricitabine (TDF/FTC) during labor significantly reduces peripartum nevirapine-associated viral drug resistance when measured by consensus HIV sequencing. It is unknown whether this effect extends to HIV subpopulations of <25-50%. We conducted a randomized trial of single-dose TDF/FTC added to peripartum nevirapine to reduce drug resistance associated with nonnucleoside reverse transcriptase inhibitors (NNRTIs). To detect mutations for NNRTIs comprising > or = 2% of the viral population, we used an oligonucleotide ligation assay (OLA) at codons 103, 106, 181, and 190 of HIV reverse transcriptase. To assess development of drug resistance mutations to our study intervention, OLA was also performed at codons 65 and 184. Among the 328 women included in the 2-week analysis, those receiving TDF/FTC were less likely to have NNRTI resistance by OLA (RR = 0.40, 95% CI = 0.21-0.77). A similar trend was observed among the 315 women included in the 6-week analysis (RR = 0.45, 95% CI = 0.31-0.66). Only two (1%) specimens had detectable K65R by OLA. Both were at 6 weeks postpartum; one was detected in the intervention arm and one in the control arm (p = 0.96). M184V was not detected. The ability of single-dose TDF/FTC to protect against peripartum NVP-induced NNRTI resistance extends to minority populations. This efficacy is achieved without significant selection of TDF- or FTC-resistant viruses.
Monitoring effectiveness of programmes to prevent mother-to-child HIV transmission in lower-income countries.
(2008-Jan) Stringer EM; Chi BH; Chintu N; Creek TL; Ekouevi DK; Coetzee D; Tih P; Boulle A; Dabis F; Shaffer N; Wilfert CM; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. eli@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Ambitious goals for paediatric AIDS control have been set by various international bodies, including a 50% reduction in new paediatric infections by 2010. While these goals are clearly appropriate in their scope, the lack of clarity and consensus around how to monitor the effectiveness of programmes to prevent mother-to-child HIV transmission (PMTCT) makes it difficult for policy-makers to mount a coordinated response. In this paper, we develop the case for using population HIV-free child survival as a gold standard metric to measure the effectiveness of PMTCT programmes, and go on to consider multiple study designs and source populations. Finally, we propose a novel community survey-based approach that could be implemented widely throughout the developing world with minor modifications to ongoing Demographic and Health Surveys.
Optimal time on HAART for prevention of mother-to-child transmission of HIV.
(2011-Oct-01) Chibwesha CJ; Giganti MJ; Putta N; Chintu N; Mulindwa J; Dorton BJ; Chi BH; Stringer JS; Stringer EM; University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA. Carla.Chibwesha@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: To determine the impact of time between initiating highly active antiretroviral therapy (HAART) and delivery-duration of antenatal HAART-on perinatal HIV infection. DESIGN: We conducted a retrospective cohort analysis of pregnant HIV-infected women in Lusaka, Zambia. Women in our cohort were receiving HAART and had an infant HIV polymerase chain reaction test between 3 and 12 weeks of life. METHODS: We examined factors associated with infant HIV infection and performed a locally weighted regression analysis to examine the effect of duration of antenatal HAART on perinatal HIV infection. RESULTS: : From January 2007 to March 2010, 1813 HIV-infected pregnant women met inclusion criteria. Mean gestational age at first antenatal visit was 21 weeks (SD ± 6), median CD4+ cell count was 231 cells per microliter (interquartile range: 164-329), and median duration of antenatal HAART was 13 weeks (interquartile range 8-19). Fifty-nine (3.3%) infants were HIV infected. Duration of antenatal HAART was the most important predictor of perinatal HIV transmission. Compared with women initiating HAART at least 13 weeks before delivery, women on HAART for ≤4 weeks had a 5.5-fold increased odds of HIV transmission (95% confidence interval: 2.6 to 11.7). Locally weighted regression analysis suggested limited additional prophylactic benefit beyond 13 weeks on antenatal HAART. CONCLUSIONS: Low rates of mother-to-child HIV transmission can be achieved within programmatic settings in Africa. Maximal effectiveness of prevention of mother-to-child transmission programs is achieved by initiating HAART at least 13 weeks before delivery.
Peripartum nevirapine exposure and subsequent clinical outcomes among HIV-infected women receiving antiretroviral therapy for at least 12 months.
(2010-Jul) Chintu N; Giganti MJ; Putta NB; Sinkala M; Sadoki E; Stringer EM; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: Prior exposure to intrapartum/neonatal nevirapine (NVP) is associated with compromised virologic treatment outcomes once non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) is initiated. We examined the longer-term clinical outcomes in a programmatic setting. METHODS: We compared post-12 month mortality and clinical treatment failure (defined by WHO clinical and immunologic criteria) among women with and without prior NVP exposure in Lusaka, Zambia. RESULTS: Between April 2004 and July 2006, 6740 women initiated an NNRTI-containing regimen. At 12 months, 5172 (78%) remained active and were included in this analysis. Of these, 596 (12%) reported prior NVP exposure, whose time from exposure to ART initiation was: <6 months for 11%, 6-12 months for 13%, >12 months for 37%, unknown for 39%. Overall, women with prior NVP exposure trended towards increased survival (adjusted hazard ratio [AHR]: 0.53; 95% confidence interval [CI]: 0.27-1.06, P = 0.07) and towards increased hazard of clinical treatment failure (AHR: 1.18; 95% CI: 0.95-1.47, P = 0.14), particularly those with exposure for <6 months (AHR: 1.52; 95% CI: 0.94-2.45, P = 0.09). CONCLUSIONS: Prior NVP exposure appeared to increase risk for clinical treatment failure after 12 months of follow-up, but this finding did not reach statistical significance. With growing evidence linking recent NVP exposure to virologic failure, optimized monitoring algorithms should be considered for women with starting NNRTI-based ART. The association between prior NVP exposure and improved survival has not been previously shown and may be a result of residual confounding around health-seeking behaviours.
Predictors of CD4 eligibility for antiretroviral therapy initiation among HIV-infected pregnant women in Lusaka, Zambia.
(2011-Aug-15) Liu KC; Mulindwa J; Giganti MJ; Putta NB; Chintu N; Chi BH; Stringer JS; Stringer EM; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. cherry.liu@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: In resource-limited settings, CD4 testing is a barrier to antiretroviral therapy initiation in pregnancy. METHODS: We used logistic regression to identify predictors of CD4 cell count ≤ 350 cells/uL in 20,233 pregnant women. RESULTS: The best-performing model included any 3 of: age ≥ 28 years old, hemoglobin ≤ 9.8 g/dL, gestational age ≤ 30 weeks, weight ≤ 64 kg, history of tuberculosis or previous death of an infant prior to one year old. Sensitivity was 45.7% (95% CI: 44.5-47.0), specificity 70.7% (95% CI: 69.6-71.8), and misclassification rate 41.4% (95% CI: 40.5-42.2). CONCLUSION: CD4 triage remains a critical element of maternal HIV care and PMTCT.
Protocol-driven primary care and community linkage to reduce all-cause mortality in rural Zambia: a stepped-wedge cluster randomized trial.
(2023) Mutale W; Ayles H; Lewis J; Bosompraph S; Chilengi R; Tembo MM; Sharp A; Chintu N; Stringer J; Society for Family Health in Zambia, Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Department of Health Policy and Management, School of Public Health, University of Zambia, Lusaka, Zambia.; University of North Carolina, Global Women Health, Chapel Hill, NC, United States.; MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Zambia AIDS Related Tuberculosis (ZAMBART), Lusaka, Zambia.
INTRODUCTION: While tremendous progress has been made in recent years to improve the health of people living in low- and middle-income countries (LMIC), significant challenges remain. Chief among these are poor health systems, which are often ill-equipped to respond to current challenges. It remains unclear whether intensive intervention at the health system level will result in improved outcomes, as there have been few rigorously designed comparative studies. We present results of a complex health system intervention that was implemented in Zambia using a cluster randomized design. METHODS: BHOMA was a complex health system intervention comprising intensive clinical training and quality improvement measures, support for commodities procurement, improved community outreach, and district level management support. The intervention was introduced as a stepped wedge cluster-randomized trial in 42 predominately rural health centers and their surrounding communities in Lusaka Province, Zambia. Baseline survey was conducted between January-May 2011, mid-line survey was conducted February-November, 2013 and Endline survey, February-November 2015.The primary outcome was all-cause mortality among those between 28 days and 60 years of age and assessed through community-based mortality surveys. Secondary outcomes included post-neonatal under-five mortality and service coverage scores. Service coverage scores were calculated across five domains (child preventative services; child treatment services; family planning; maternal health services, and adult health services). We fit Cox proportional hazards model with shared frailty at the cluster level for the primary analysis. Mortality rates were age-standardized using the WHO World Standard Population. RESULTS: Mortality declined substantially from 3.9 per 1,000 person-years in the pre-intervention period, to 1.5 per 1,000 person-years in the post intervention period. When we compared intervention and control periods, there were 174 deaths in 49,230 person years (age-standardized rate = 4.4 per 1,000 person-years) in the control phase and 277 deaths in 74,519 person years (age-standardized rate = 4.6 per 1,000 person-years) in the intervention phase. Overall, there was no evidence for an effect of the intervention in minimally-adjusted [hazard ratio (HR) = 1.18; 95% confidence interval (CI): 0.88, 1.56; value of CONCLUSION: We noted an overall reduction in post-neonatal under 60 mortality in the study communities during the period of our study, but this could not be attributed to the BHOMA intervention. Some improvements in service coverage scores were observed. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, Identifier NCT01942278.
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.
(2007-Nov-17) Chi BH; Sinkala M; Mbewe F; Cantrell RA; Kruse G; Chintu N; Aldrovandi GM; Stringer EM; Kankasa C; Safrit JT; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Intrapartum and neonatal single-dose nevirapine are essential components of perinatal HIV prevention in resource-constrained settings, but can induce resistance to other non-nucleoside reverse transcriptase inhibitor drugs. We aimed to investigate whether this complication would be reduced with a single peripartum intervention of tenofovir and emtricitabine. METHODS: We randomly assigned 400 HIV-infected pregnant women who sought care at two public-sector primary health facilities in Lusaka, Zambia. One was excluded, 200 were assigned to receive a single oral dose of 300 mg tenofovir disoproxil fumarate with 200 mg emtricitabine under direct observation, and 199 to receive no study drug. Short-course zidovudine and intrapartum nevirapine were offered to all HIV-infected women, according to the local standard of care. Women who met national criteria for antiretroviral therapy were referred for care and not enrolled. Our primary study outcome was resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery. We used standard population sequencing to determine HIV genotypes. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00204308. FINDINGS: Of the 200 women who were randomly assigned to the intervention, 14 were lost to follow-up or withdrew from the study, two did not take study drug according to protocol, and one specimen was lost; 23 of 199 controls were lost to follow-up or withdrew from the study, and three specimens were lost. Women given the intervention were 53% less likely than controls to have a mutation that conferred resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery (20/173 [12%] vs 41/166 [25%]; risk ratio [RR] 0.47, 95% CI 0.29-0.76). We noted postpartum anaemia, the most common serious adverse event in mothers, in four women in each group. 20 of 198 (10%) infants in the intervention group and 23 of 199 (12%) controls had a serious adverse event, mostly due to septicaemia (n=22) or pneumonia (n=8); these events did not differ between groups, and none were judged to be caused by the study intervention. INTERPRETATION: A single dose of tenofovir and emtricitabine at delivery reduced resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery by half; therefore this treatment should be considered as an adjuvant to intrapartum nevirapine.