Achieving HIV Epidemic Control and Improving Maternal Healthcare Services with Community-Based HIV Service Delivery in Zambia: Mixed-Methods Assessment of the SMACHT Project.

Novel community-based approaches are needed to achieve and sustain HIV epidemic control in Zambia. Under the Stop Mother and Child HIV Transmission (SMACHT) project, the Community HIV Epidemic Control (CHEC) differentiated service delivery model used community health workers to support HIV testing, ART linkage, viral suppression, and prevention of mother-to-child transmission (MTCT). A multi-methods assessment included programmatic data analysis from April 2015 to September 2020, and qualitative interviews from February to March 2020. CHEC provided HIV testing services to 1,379,387 clients; 46,138 were newly identified as HIV-positive (3.3% yield), with 41,366 (90%) linked to ART. By 2020, 91% (60,694/66,841) of clients on ART were virally suppressed. Qualitatively, healthcare workers and clients benefitted from CHEC, with provision of confidential services, health facility decongestion, and increased HIV care uptake and retention. Community-based models can increase uptake of HIV testing and linkage to care, and help achieve epidemic control and elimination of MTCT.

Effect of Enhanced Adherence Package on Early ART Uptake Among HIV-Positive Pregnant Women in Zambia: An Individual Randomized Controlled Trial.

We evaluated the effect of an option B-plus Enhanced Adherence Package (BEAP), on early ART uptake in a randomized controlled trial. HIV-positive, ART naïve pregnant women in Lusaka, Zambia, were randomized to receive BEAP (phone calls/home visits, additional counseling, male partner engagement and missed-visit follow-up) versus standard of care (SOC). The primary outcome was initiating and remaining on ART at 30 days. Analysis was by intention to treat (ITT) using logistic regression. Additional per protocol analysis was done. We enrolled 454 women; 229 randomized to BEAP and 225 to SOC. Within 30 days of eligibility, 445 (98.2%) initiated ART. In ITT analysis, 82.5% BEAP versus 80.4% SOC participants reached primary outcome (crude relative risk [RR] 1.03; 95% confidence interval [CI] 0.91-1.16; Wald test statistic = 0.44; p-value = 0.66). In per protocol analysis, (92 participants (40.2%) excluded), 91.9% BEAP versus 80.4% SOC participants reached primary outcome (crude RR 1.14; 95% CI 1.02-1.29; Wald test statistic = 2.23; p-value = 0.03). Early ART initiation in pregnancy was nearly universal but there was early drop out suggesting need for additional adherence support.This trial was registered at ClinicalTrials.gov (trials number NCT02459678) on May 14, 2015.

Urban-rural disparities in treatment outcomes among recurrent TB cases in Southern Province, Zambia.

BACKGROUND: At least 13-20% of all Tuberculosis (TB) cases are recurrent TB. Recurrent TB has critical public health importance because recurrent TB patients have high risk of Multi-Drug Resistant TB (MDR-TB). It is critical to understand variations in the prevalence and treatment outcomes of recurrent TB between different geographical settings. The objective of our study was to estimate the prevalence of recurrent TB among TB cases and compare risk of unfavorable treatment outcomes between rural and urban settings. METHODS: In a retrospective cohort study conducted in southern province of Zambia, we used mixed effects logistic regression to asses associations between explanatory and outcome variables. Primary outcome was all-cause mortality and exposure was setting (rural/urban). Data was abstracted from the facility TB registers. RESULTS: Overall 3566 recurrent TB cases were diagnosed among 25,533 TB patients. The prevalence of recurrent TB was 15.3% (95% CI: 14.8 15.9) in urban and 11.3% (95% CI: 10.7 12.0) in rural areas. Death occurred in 197 (5.5%), 103 (2.9%) were lost to follow-up, and 113 (3.2%) failed treatment. Rural settings had 70% higher risk of death (adjusted OR: 1.7; 95% CI: 1.2 2.7). Risk of lost to follow-up was twice higher in rural than urban (adjusted OR: 2.0 95% CI: 1.3 3.0). Compared to HIV-uninfected, HIV-infected individuals on Antiretroviral Treatment (ART) were 70% more likely to die (adjusted OR: 1.7; 95% CI: 1.2 3.1). CONCLUSION: Recurrent TB prevalence was generally high in both urban and rural settings. The risk of mortality and lost to follow-up was higher among rural patients. We recommend a well-organized Directly Observed Therapy strategy adapted to setting where heightened TB control activities are focused on areas with poor treatment outcomes.

Clinical management of children with fever: a cross-sectional study of quality of care in rural Zambia.

OBJECTIVE: To evaluate current practices and standards of evaluation and treatment of childhood febrile illness in Southern Province, Zambia. METHODS: From November to December 2013, we conducted a cross-sectional survey of facilities and health workers and we observed the health workers' interactions with febrile children and their caregivers. The facility survey recorded level of staffing, health services provided by the facility, availability and adequacy of medical equipment, availability of basic drugs and supplies and availability of treatment charts and guidelines. The health worker survey assessed respondents' training, length of service, access to national guidelines and job aids for managing illnesses, and their practice and knowledge on management of neonatal and child illnesses. We also conducted exit interviews with caregivers to collect information on demographic characteristics, chief complaints, counselling and drug dispensing practices. FINDINGS: This study included 24 health facilities, 53 health workers and 161 children presenting with fever. Facilities were insufficiently staffed, stocked and equipped to adequately manage childhood fever. Children most commonly presented with upper respiratory tract infections (46%; 69), diarrhoea (31%; 27) and malaria (10%; 16). Health workers insufficiently evaluated children for danger signs, and less than half (47%; 9/19) of children with pneumonia received appropriate antibiotic treatment. Only 57% (92/161) were tested for malaria using either rapid diagnostic tests or microscopy. CONCLUSION: Various health system challenges resulted in a substantial proportion of children receiving insufficient management and treatment of febrile illness. Interventions are needed including strengthening the availability of commodities and improving diagnosis and treatment of febrile illness.

Outbreak of Plague in a High Malaria Endemic Region - Nyimba District, Zambia, March-May 2015.

Outbreaks of plague have been recognized in Zambia since 1917 (1). On April 10, 2015, Zambia's Ministry of Health was notified by the Eastern Provincial Medical Office of possible bubonic plague cases in Nyimba District. Eleven patients with acute fever and cervical lymphadenopathy had been evaluated at two rural health centers during March 28-April 9, 2015; three patients died. To confirm the outbreak and develop control measures, the Zambia Ministry of Health's Field Epidemiology Training Program (ZFETP) conducted epidemiologic and laboratory investigations in partnership with the University of Zambia's schools of Medicine and Veterinary Medicine and the provincial and district medical offices. Twenty-one patients with clinically compatible plague were identified, with symptom onset during March 26-May 5, 2015. The median age was 8 years, and all patients were from the same village. Blood specimens or lymph node aspirates from six (29%) patients tested positive for Yersinia pestis by polymerase chain reaction (PCR). There is an urgent need to improve early identification and treatment of plague cases. PCR is a potential complementary tool for identifying plague, especially in areas with limited microbiologic capacity. Twelve (57%) patients, including all six with PCR-positive plague and all three who died, also tested positive for malaria by rapid diagnostic test (RDT). Plague patients coinfected with malaria might be misdiagnosed as solely having malaria, and appropriate antibacterial treatment to combat plague might not be given, increasing risk for mortality. Because patients with malaria might be coinfected with other pathogens, broad spectrum antibiotic treatment to cover other pathogens is recommended for all children with severe malaria, until a bacterial infection is excluded.

Antiretroviral therapy improves survival among TB-HIV co-infected patients who have CD4+ T-cell count above 350cells/mm3.

BACKGROUND: Co-infection with Mycobacterium tuberculosis remains a leading cause of morbidity and mortality among HIV infected individuals especially in developing countries. Early initiation of cART in these patients when CD4+ T cell count is less than 200cells/mm3 has reduced disease progression and mortality. However for patients with higher CD4+ T cell counts greater than 350cells/mm3 evidence is conflicting. In this study we seek to evaluate the effectiveness of cART in reducing mortality among TB-HIV co-infected patients with CD4 + T cells above 350cells/mm3 at the time of TB diagnosis. METHOD: In a retrospective cohort study we analyzed 337 HIV-TB co-infected patients with CD4+ T cells above 350cells/mm3 at baseline who were diagnosed between 2006 and 2012 in the southern province of Zambia. The primary outcome was all-cause mortality. We estimated the effect of cART by comparing survival according to cART and controlling for differential loss to follow-up. RESULTS: Of the 257 patients on cART, 22 died (9 %) and 20 (8 %) were lost to follow-up; of 80 patients not on cART, 20 died (25 %) and 19 (24 %) were lost to follow-up. Patients treated with cART had better survival compared to those not treated (P < 0 · 0001, log-rank test). In a proportional hazard regression adjusting for Cotrimoxazole, the risk of death was reduced by 78 % with cART (95 % CI: 0 · 47, 0 · 91). In a propensity score analysis, the effect of cART was still beneficial. CONCLUSION: In patients with HIV-associated TB and CD4+ T cells above 350cells/mm3, treatment with cART reduced mortality for up to 4 years as compared to no cART and was associated with better retention in care.

Pediatric and adolescent HIV viral load coverage and suppression rates in the context of the COVID-19 pandemic in 12 PEPFAR-supported sub-Saharan African countries in 2019 and 2020.

The early period of the COVID-19 pandemic limited access to HIV services for children and adolescents living with HIV (C/ALHIV). To determine progress in providing care and treatment services, we describe viral load coverage (VLC) and suppression (VLS) (<1000 copies/ mL) rates during the COVID-19 pandemic in 12 United States President's Emergency Plan for AIDS Relief (PEPFAR)-supported countries. Data for children (0-9 years) and adolescents (10-19 years) on VLC and VLS were analyzed for 12 sub-Saharan African (SSA) countries between 2019 (pre-COVID-19) and 2020 (during COVID-19). We report the number of viral load (VL) tests, and percent change in VLC and VLS for patients on ART. For 12 countries, 181,192 children had a VL test during the pre-COVID-19 period compared with 177,683 December 2020 during COVID-19. VLC decreased from 68.8% to 68.3% overall. However, 9 countries experienced an increase ranging from a 0.7%-point increase for Tanzania and Zimbabwe to a 15.3%-point increase for Nigeria. VLS increased for all countries from 71.2% to 77.7%. For adolescents the number with a VL test increased from 377,342 to 402,792. VLC decreased from 77.4% to 77.1%. However, 7 countries experienced an increase ranging from 1.8% for Mozambique to 13.8% for Cameroon. VLS increased for all countries from 76.8% to 83.8%. This analysis shows variation in HIV VLC across 12 SSA countries. VLS consistently improved across all countries demonstrating resilience of countries during 2020. Countries should continue to improve clinical outcomes from C/ALHIV despite service disruptions that may occur during pandemic response.

Intended versus actual delivery location and factors associated with change in delivery location among pregnant women in Southern Province, Zambia: a prespecified secondary observational analysis of the ZamCAT.

OBJECTIVES: This prespecified, secondary analysis of the Zambia Chlorhexidine Application Trial (ZamCAT) aimed to determine the proportion of women who did not deliver where they intended, to understand the underlying reasons for the discordance between planned and actual delivery locations; and to assess sociodemographic characteristics associated with concordance of intention and practice. DESIGN: Prespecified, secondary analysis from randomised controlled trial. SETTING: Recruitment occurred in 90 primary health facilities (HFs) with follow-up in the community in Southern Province, Zambia. PARTICIPANTS: Between 15 February 2011 and 30 January 2013, 39 679 pregnant women enrolled in ZamCAT. SECONDARY OUTCOME MEASURES: The location where mothers gave birth (home vs HF) was compared with their planned delivery location. RESULTS: When interviewed antepartum, 92% of respondents intended to deliver at an HF, 6.1% at home and 1.2% had no plan. However, of those who intended to deliver at an HF, 61% did; of those who intended to deliver at home, only 4% did; and of those who intended to deliver at home, 2% delivered instead at an HF. Among women who delivered at home, women who were aged 25-34 and ≥35 years were more likely to deliver where they intended than women aged 20-24 years (adjusted OR (aOR)=1.31, 95% CI=1.11 to 1.50 and aOR=1.32, 95% CI=1.12 to 1.57, respectively). Women who delivered at HFs had greater odds of delivering where they intended if they received any primary schooling (aOR=1.34, 95% CI=1.09 to 1.72) or more than a primary school education (aOR=1.54, 95% CI=1.17 to 2.02), were literate (aOR=1.33, 95% CI=1.119 to 1.58), and were not in the lowest quintile of the wealth index. CONCLUSION: Discrepancies between intended and actual delivery locations highlight the need to go beyond the development of birth plans and exposure to birth planning messaging. More research is required to address barriers to achieving intentions of a facility-based childbirth. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT01241318).

The impact of a multi-level maternal health programme on facility delivery and capacity for emergency obstetric care in Zambia.

In 2012, Saving Mothers, Giving Life (SMGL), a multi-level health systems initiative, launched in Kalomo District, Zambia, to address persistent challenges in reducing maternal mortality. We assessed the impact of the programme from 2012 to 2013 using a quasi-experimental study with both household- and health facility-level data collected before and after implementation in both intervention and comparison areas. A total of 21,680 women and 75 non-hospital health centres were included in the study. Using the difference-in-differences method, multivariate logistic regression, and run charts, rates of facility-based birth (FBB) and delivery with a skilled birth provider were compared between intervention and comparison sites. Facility capacity to provide emergency obstetric and newborn care was also assessed before and during implementation in both study areas. There was a 45% increase in the odds of FBB after the programme was implemented in Kalomo relative to comparison districts, but there was a limited measurable change in supply-side indicators of intrapartum maternity care. Most facility-level changes related to an increase in capacity for newborn care. As SMGL and similar programmes are scaled-up and replicated, our results underscore the need to ensure that the health services supply is in balance with improved demand to achieve maximal reductions in maternal mortality.

Identifying Gaps in Prevention of Mother to Child Transmission of HIV: A Case Series of HIV-positive Infants in Zambia.

BACKGROUND: To determine the timing of prevention of mother-to-child transmission cascade programmatic barriers to understand the service gaps in preparation for scale up of Option B+ in the Southern Province of Zambia. METHODS: A database search of the National Dried Blood Spot Registry in Zambia for DNA polymerase chain reaction identified human immunodeficiency virus (HIV)-infected infants from 5 facilities in 2 districts in Southern Province, Zambia over a 6-month observation period (January 2013 to June 2013). RESULTS: Seventeen HIV-positive infants out of 459 infants tested were identified from 5 health facilities that provided antiretroviral therapy (ART) initiation within the antenatal care (ANC) clinic, for a transmission rate of 3.7%. Possible risk factors identified for mother to child transmission of HIV included late ANC presentation, home delivery, provision of maternal short course prophylaxis, maternal refusal to initiate treatment and loss to follow-up. CONCLUSIONS: As Zambia transitions to life-long combination ART initiation for HIV-positive pregnant women under Option B+, and subsequent ART integration into ANC facilities, it is crucial to understand prevention of mother-to-child transmission program gaps to achieve the goal of eliminating mother to child transmission of HIV in Zambia.

Effectiveness of 4% chlorhexidine umbilical cord care on neonatal mortality in Southern Province, Zambia (ZamCAT): a cluster-randomised controlled trial.

BACKGROUND: Chlorhexidine umbilical cord washes reduce neonatal mortality in south Asian populations with high neonatal mortality rates and predominantly home-based deliveries. No data exist for sub-Saharan African populations with lower neonatal mortality rates or mostly facility-based deliveries. We compared the effect of chlorhexidine with dry cord care on neonatal mortality rates in Zambia. METHODS: We undertook a cluster-randomised controlled trial in Southern Province, Zambia, with 90 health facility-based clusters. We enrolled women who were in their second or third trimester of pregnancy, aged at least 15 years, and who would remain in the catchment area for follow-up of 28 days post-partum. Newborn babies received clean dry cord care (control) or topical application of 10 mL of a 4% chlorhexidine solution once per day until 3 days after cord drop (intervention), according to cluster assignment. We used stratified, restricted randomisation to divide clusters into urban or two rural groups (located <40 km or ≥40 km to referral facility), and randomly assigned clusters (1:1) to use intervention (n=45) or control treatment (n=45). Sites, participants, and field monitors were aware of their study assignment. The primary outcomes were all-cause neonatal mortality within 28 days post-partum and all-cause neonatal mortality within 28 days post-partum among babies who survived the first 24 h of life. Analysis was by intention to treat. Neonatal mortality rate was compared with generalised estimating equations. This study is registered at ClinicalTrials.gov (NCT01241318). FINDINGS: From Feb 15, 2011, to Jan 30, 2013, we screened 42 356 pregnant women and enrolled 39 679 women (mean 436·2 per cluster [SD 65·3]), who had 37 856 livebirths and 723 stillbirths; 63·8% of deliveries were facility-based. Of livebirths, 18 450 (99·7%) newborn babies in the chlorhexidine group and 19 308 (99·8%) newborn babies in the dry cord care group were followed up to day 28 or death. 16 660 (90·0%) infants in the chlorhexidine group had chlorhexidine applied within 24 h of birth. We found no significant difference in neonatal mortality rate between the chlorhexidine group (15·2 deaths per 1000 livebirths) and the dry cord care group (13·6 deaths per 1000 livebirths; risk ratio [RR] 1·12, 95% CI 0·88-1·44). Eliminating day 0 deaths yielded similar findings (RR 1·12, 95% CI 0·86-1·47). INTERPRETATION: Despite substantial reductions previously reported in south Asia, chlorhexidine cord applications did not significantly reduce neonatal mortality rates in Zambia. Chlorhexidine cord applications do not seem to provide clear benefits for newborn babies in settings with predominantly facility-based deliveries and lower (<30 deaths per 1000 livebirths) neonatal mortality rates. FUNDING: Bill & Melinda Gates Foundation.

The state of routine and emergency obstetric and neonatal care in Southern Province, Zambia.

OBJECTIVE: To evaluate the capacity of health facilities in Southern Province, Zambia, to perform routine obstetric care and emergency obstetric and neonatal care (EmONC). METHODS: Surveys were completed at 90 health centers and 10 hospitals between September 1, 2011, and February 28, 2012. An expanded set of signal functions for routine care and EmONC was used to assess the facilities' capacity to provide obstetric and neonatal care. RESULTS: Interviews were completed with 172 health workers. Comprehensive EmONC was available in only six of 10 hospitals; the remaining four hospitals did not perform all basic EmONC signal functions. None of the 90 health centers performed the basic set of EmONC signal functions. Performance of routine obstetric care functions, health worker EmONC training, and facility infrastructure and staffing varied. CONCLUSION: Assessment of the indicators for routine care revealed that several low-cost interventions are currently underused in Southern Province. There is substantial room for improvement in emergency and routine obstetric and neonatal care at the surveyed facilities. Efforts should focus on improving infrastructure and supplies, EmONC training, and adherence to the UN guidelines for routine and emergency obstetric care.

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.

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.

Engagement of the community, traditional leaders, and public health system in the design and implementation of a large community-based, cluster-randomized trial of umbilical cord care in Zambia.

Conducting research in areas with diverse cultures requires attention to community sensitization and involvement. The process of community engagement is described for a large community-based, cluster-randomized, controlled trial comparing daily 4% chlorhexidine umbilical cord wash to dry cord care for neonatal mortality prevention in Southern Province, Zambia. Study preparations required baseline formative ethnographic research, substantial community sensitization, and engagement with three levels of stakeholders, each necessitating different strategies. Cluster-specific birth notification systems developed with traditional leadership and community members using community-selected data collectors resulted in a post-natal home visit within 48 hours of birth in 96% of births. Of 39,679 pregnant women enrolled (93% of the target of 42,570), only 3.7% were lost to follow-up or withdrew antenatally; 0.2% live-born neonates were lost by day 28 of follow-up. Conducting this trial in close collaboration with traditional, administrative, political, and community stakeholders facilitated excellent study participation, despite structural and sociocultural challenges.

Elimination of Mother-To-Child Transmission of HIV Infection: The Drug Resource Enhancement against AIDS and Malnutrition Model.

The Drug Resource Enhancement against AIDS and Malnutrition Program (DREAM) gathered professionals in the field of Elimination of HIV-Mother-To-Child Transmission (EMTCT) in Maputo in 2013 to discuss obstacles and solutions for the elimination of HIV vertical transmission in sub-Saharan Africa. During this workshop, the benefits of administrating combined antiretroviral therapy (cART) to HIV positive women from pregnancy throughout breastfeeding were reviewed. cART is capable of reducing vertical transmission to less than 5% at 24 months of age, as well as maternal mortality and infant mortality in both HIV infected and exposed populations to levels similar to those of uninfected individuals. The challenge for programs targeting eMTCT in developing countries is retention in care and treatment adherence. Both are intrinsically related to the model of care. The drop-out from eMTCT programs before cART initiation ranges from 33%-88% while retention rates at 18-24 months are less than 50%. Comprehensive strategies including peer-to-peer education, social support and laboratory monitoring can reduce refusals to less than 5% and attain retention rates approaching 90%. Several components of the model of care for reduction of HIV-1 MTCT are feasible and implementable in scale-up strategies. A review of this model of care for HIV eMTCT is provided.