"Why has this new vaccine come and for what reasons?" key antecedents and questions for acceptance of a future maternal GBS vaccine: Perspectives of pregnant women, lactating women, and community members in Kenya.

Group B streptococcus (GBS) is a leading global cause of neonatal sepsis and meningitis, stillbirth, and puerperal sepsis. While intrapartum antibiotic prophylaxis (IAP) is a currently available GBS disease prevention strategy, IAP is programmatically complex to implement, precluding use in low- and middle-income countries. In Kenya, 2% of stillbirths are attributable to GBS infection. Two maternal GBS vaccines are in late-stage clinical development. However, licensure of a maternal GBS vaccine does not translate into reduction of disease. We conducted 28 in-depth interviews with pregnant people, lactating people, and community members across two counties in Kenya to better understand the attitudes and informational needs of primary vaccine beneficiaries. We identified two emerging themes from the data. The first focused on antecedents to maternal GBS vaccine acceptability. The most common antecedents focused on the vaccine's ability to protect the baby and/or the mother, followed by community sensitization before the vaccine was available. The second key theme focused on questions that would need to be addressed before someone could accept a maternal GBS vaccine. Three key categories of questions were identified, including vaccine safety compared to vaccine benefits, who gets the vaccine, and how the vaccine works. Realizing the potential benefits of a future GBS maternal vaccine will require a multifactorial approach, including ensuring that communities are aware of GBS-related harms as well as the safety and effectiveness of a maternal GBS vaccine. Our study contributes to informing this multifactorial approach by elucidating the attitudes and concerns of key populations.

Documenting the development, adoption and pre-ebola implementation of Liberia's integrated disease surveillance and response (IDSR) strategy.

BACKGROUND: In the immediate aftermath of a 14-year civil conflict that disrupted the health system, Liberia adopted the internationally recommended integrated disease surveillance and response (IDSR) strategy in 2004. Despite this, Liberia was among the three West African countries ravaged by the worst Ebola epidemic in history from 2014 to 2016. This paper describes successes, failures, strengths, and weaknesses in the development, adoption, and implementation of IDSR following the civil war and up until the outbreak of Ebola, from 2004 to early 2014. METHODS: We reviewed 112 official Government documents and peer-reviewed articles and conducted 29 in-depth interviews with key informants from December 2021 to March 2022 to gain perspectives on IDSR in the post-conflict and pre-Ebola era in Liberia. We assessed the core and supportive functions of IDSR, such as notification of priority diseases, confirmation, reporting, analysis, investigation, response, feedback, monitoring, staff training, supervision, communication, and financial resources. Data were triangulated and presented via emerging themes and in-depth accounts to describe the context of IDSR introduction and implementation, and the barriers surrounding it. RESULTS: Despite the adoption of the IDSR framework, Liberia failed to secure the resources-human, logistical, and financial-to support effective implementation over the 10-year period. Documents and interview reports demonstrate numerous challenges prior to Ebola: the surveillance system lacked key components of IDSR including laboratory testing capacity, disease reporting, risk communication, community engagement, and staff supervision systems. Insufficient financial support and an abundance of vertical programs further impeded progress. In-depth accounts by donors and key governmental informants demonstrate that although the system had a role in detecting Ebola in Liberia, it could not respond effectively to control the disease. CONCLUSION: Our findings suggest that post-war, Liberia's health system intended to prioritize epidemic preparedness and response with the adoption of IDSR. However, insufficient investment and systems development meant IDSR was not well implemented, leaving the country vulnerable to the devastating impact of the Ebola epidemic.

The Evolving Pediatric HIV Epidemic in Rural Southern Zambia: The Beneficial Impact of Advances in Prevention and Treatment at a District Hospital From 2007 to 2019.

BACKGROUND: Remarkable progress has been made in expanding access to services addressing the pediatric HIV epidemic, including programs to prevent mother-to-child transmission, early diagnosis and treatment for children living with HIV. Few long-term data are available from rural sub-Saharan Africa to assess implementation and impact of national guidelines. METHODS: Results from 3 cross-sectional studies and 1 cohort study conducted at Macha Hospital in Southern Province, Zambia from 2007 to 2019 were summarized. For infant diagnosis, maternal antiretroviral treatment, infant test results and turnaround times for results were evaluated by year. For pediatric HIV care, the number and age of children initiating care and treatment, and treatment outcomes within 12 months were evaluated by year. RESULTS: Receipt of maternal combination antiretroviral treatment increased from 51.6% in 2010-2012 to 93.4% in 2019, and the proportion of infants testing positive decreased from 12.4% to 4.0%. Turnaround times for results returning to clinic varied but were shorter when labs consistently used a text messaging system. The proportion of mothers receiving results was higher when a text message intervention was piloted. The number of children living with HIV enrolled into care and the proportion initiating treatment with severe immunosuppression and dying within 12 months decreased over time. CONCLUSIONS: These studies demonstrate the long-term beneficial impact of implementing a strong HIV prevention and treatment program. While expansion and decentralization brought challenges, the program succeeded in decreasing the rate of mother-to-child transmission and ensuring that children living with HIV benefit from access to life-saving treatment.

Scientific Findings of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

For a decade, the Southern and Central Africa International Center of Excellence for Malaria Research has operated with local partners across study sites in Zambia and Zimbabwe that range from hypo- to holoendemic and vary ecologically and entomologically. The burden of malaria and the impact of control measures were assessed in longitudinal cohorts, cross-sectional surveys, passive and reactive case detection, and other observational designs that incorporated multidisciplinary scientific approaches: classical epidemiology, geospatial science, serosurveillance, parasite and mosquito genetics, and vector bionomics. Findings to date have helped elaborate the patterns and possible causes of sustained low-to-moderate transmission in southern Zambia and eastern Zimbabwe and recalcitrant high transmission and fatality in northern Zambia. Cryptic and novel mosquito vectors, asymptomatic parasite reservoirs in older children, residual parasitemia and gametocytemia after treatment, indoor residual spraying timed dyssynchronously to vector abundance, and stockouts of essential malaria commodities, all in the context of intractable rural poverty, appear to explain the persistent malaria burden despite current interventions. Ongoing studies of high-resolution transmission chains, parasite population structures, long-term malaria periodicity, and molecular entomology are further helping to lay new avenues for malaria control in southern and central Africa and similar settings.

Policy Implications of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

The International Centers of Excellence for Malaria Research (ICEMR) were established by the National Institute of Allergy and Infectious Diseases more than a decade ago to provide multidisciplinary research support to malaria control programs worldwide, operating in endemic areas and contributing technology, expertise, and ultimately policy guidance for malaria control and elimination. The Southern and Central Africa ICEMR has conducted research across three main sites in Zambia and Zimbabwe that differ in ecology, entomology, transmission intensity, and control strategies. Scientific findings led to new policies and action by the national malaria control programs and their partners in the selection of methods, materials, timing, and locations of case management and vector control. Malaria risk maps and predictive models of case detection furnished by the ICEMR informed malaria elimination programming in southern Zambia, and time series analyses of entomological and parasitological data motivated several major changes to indoor residual spray campaigns in northern Zambia. Along the Zimbabwe-Mozambique border, temporal and geospatial data are currently informing investigations into a recent resurgence of malaria. Other ICEMR findings pertaining to parasite and mosquito genetics, human behavior, and clinical epidemiology have similarly yielded immediate and long-term policy implications at each of the sites, often with generalizable conclusions. The ICEMR programs thereby provide rigorous scientific investigations and analyses to national control and elimination programs, without which the impediments to malaria control and their potential solutions would remain understudied.

Factors associated with antiretroviral therapy use among pregnant women in rural and urban settings in Southern Province, Zambia: 2016-2019.

OBJECTIVES: To assess antiretroviral therapy (ART) coverage among pregnant women living with HIV and compare the characteristics of women who received and did not receive ART during pregnancy in Zambia. METHODS: A cross-sectional study was conducted at urban and rural health facilities in Southern Province, Zambia, from 2016 to 2019. Pregnant women living with HIV delivering at study sites were enrolled and administered a questionnaire, and the results of infant diagnostic testing for HIV at birth was documented. RESULTS: About 1184 mother/infant pairs were enrolled. ART coverage was 93.7%. Most women who did not receive ART during pregnancy reported HIV diagnosis at delivery (18.0%) or during pregnancy (57.7%). The primary reported reason for not receiving ART was not wanting to take the drugs. Women who did not receive ART during pregnancy were significantly younger, less likely to have disclosed their HIV-infection status to others, and less likely to have received antenatal care than women who received ART. ART use correlated with higher levels of education in urban but not rural sites. Overall, 1.0% of infants were infected with HIV at birth, including 0.8% of infants born to women who received ART and 4.1% of infants born to women who did not. CONCLUSIONS: Most women received ART according to guidelines, resulting in low perinatal transmission rates of HIV to infants. Efforts to increase ART coverage and prevent vertical transmission should focus on identifying incident HIV infections during pregnancy and strengthening counselling for newly diagnosed pregnant women.

The Unmeasured Burden of Febrile, Respiratory, and Diarrheal Illnesses Identified Through Active Household Surveillance in a Low Malaria Transmission Setting in Southern Zambia.

Malaria incidence has declined in southern Zambia over recent decades, leading to efforts to achieve and sustain malaria elimination. Understanding the remaining disease burden is key to providing optimal health care. A longitudinal study conducted in a rural area of Choma District, Southern Province, Zambia, assessed the prevalence of and factors associated with symptoms of non-malarial illnesses and treatment-seeking behavior. We analyzed data collected monthly between October 2018 through September 2020 from 1,174 individuals from 189 households. No incident malaria cases were detected by rapid diagnostic tests among febrile participants. Mixed-effects logistic regression identified factors associated with cough, fever, diarrhea, and treatment-seeking. Incidence rates of cough (192 of 1,000 person-months), fever (87 of 1,000 person-months), and fever with cough (37 of 1,000 person-months) were highest among adults older than 65 years. Diarrhea incidence (37 of 1,000 person-months) was highest among children younger than 5 years. For every additional symptomatic household member, one's odds of experiencing symptoms increased: cough by 47% (95% CI, 40-55), fever by 31% (95% CI, 23-40), diarrhea by 31% (95% CI, 17-46), and fever with cough by 112% (95% CI, 90-137), consistent with household clustering of illnesses. However, between 35% and 75% of participants did not seek treatment for their symptoms. Treatment-seeking was most common for children 5 to 9 years old experiencing diarrhea (adjusted odds ratio, 3.61; 95% CI, 1.42-9.18). As malaria prevalence reduces, respiratory and diarrheal infections persist, particularly among young children but, notably, also among adults older than 65 years. Increasing awareness of the disease burden and treatment-seeking behavior are important for guiding resource re-allocation as malaria prevalence declines in this region.

Treatment outcomes among children younger than five years living with HIV in rural Zambia, 2008-2018: a cohort study.

BACKGROUND: HIV testing and treatment guidelines for children in sub-Saharan Africa have evolved over time, such that children are now treated at younger ages. The objective of this study was to describe the treatment experience for immunologic, virologic, and growth outcomes among HIV-infected Zambian children younger than 5 years of age from 2008 to 2018. METHODS: Participants enrolled in a clinical cohort study in Macha, Zambia and initiating antiretroviral treatment before 5 years of age between 2008 and 2015 were included in the analysis and followed up to the end of 2018. Outcomes, including growth, CD4+ T-cell percentage, viral suppression, and mortality, were evaluated among all children using longitudinal and survival analyses. Comparisons by age at treatment initiation (< 1, 1 to < 2, and 2 to < 5 years) were also evaluated. RESULTS: Three hundred eighty-one children initiating treatment before 5 years of age between 2008 and 2015 were included in the analysis. Growth metrics and CD4+ T-cell percentage improved over time after treatment initiation. However, 20% of children remained underweight and 40% of children remained stunted after the first 36 months of treatment. 85% of children had a viral load < 400 copies/mL after 12 months of treatment. However, children < 1 year at treatment initiation were more likely to have a detectable viral load in the first 12 months of treatment and less likely to achieve viral suppression compared to older children. Mortality was highest in the first 12 months of treatment, among underweight children, and among children initiating treatment in 2008-2010 compared to 2011-2015. CONCLUSIONS: Most children initiating antiretroviral treatment from 2008 to 2015 in rural Zambia responded well to treatment. However, many children remained underweight and stunted, and experienced high mortality rates during the first few months of treatment. This supports continued efforts to improve early infant diagnosis, nutritional support, and pediatric drug formulations.

The NSEBA Demonstration Project: implementation of a point-of-care platform for early infant diagnosis of HIV in rural Zambia.

OBJECTIVES: To describe the experience and resource requirements of implementing point-of-care testing for early infant diagnosis of HIV in rural Zambia. METHODS: A demonstration project was conducted using a hub-and-spoke model in 2018-2019 at five clinics in rural Zambia. Two testing hubs were established, and all HIV-exposed infants were tested with the GeneXpert system. Data on costs, turnaround times and test results were collected. RESULTS: Seven hundred and eighty six tests were conducted. At the hubs, results were available a median of 2.4 (IQR: 2.1, 2.8) hours after sample collection and most mothers (84%) received same-day results. At the spoke facilities, results were available a median of 9 days (IQR: 7, 12) after sample collection and provided to the mother a median of 16 days (IQR: 10, 28) after sample collection. Eleven children tested positive, and 9 (82%) started treatment a median of 13 days (IQR: 7, 21) after sample collection and on the day mothers received results. In contrast, results from matching samples sent for routine testing were available a median of 38 days (IQR: 27, 61) after sample collection and provided to the mother a median of 91 days (IQR: 47, 135) after sample collection. CONCLUSIONS: Implementing point-of-care testing in a network of rural health centres in Zambia required significant initial and ongoing investment in infrastructure, training and supervision. However, point-of-care testing can rapidly diagnose HIV-infected infants, so they can benefit from early treatment.

House Structure Is Associated with Malaria among Febrile Patients in a High-Transmission Region of Zambia.

Since the late nineteenth century, the importance of house structure as a determinant of malaria risk has been recognized. Few studies to date have examined the association of housing and malaria in clinical populations. We conducted a cross-sectional study of febrile patients (n = 282) at two rural health clinics in a high malaria-transmission area of northern Zambia. Participants underwent testing for Plasmodium falciparum infection by PCR. Demographic and other risk factors including house structure, indoor residual spraying (IRS), bed net use, education level, and household income were collected. Data were fitted to logistic regression models for relational and mediation analyses. Residing in a house with a thatch roof was associated with higher odds of malaria than residing in a house with corrugated metal (odds ratio: 2.6; 95% CI: 1.0-6.3, P = 0.04). Lower income and educational attainment were also associated with greater odds of malaria. Living under a thatch roof accounted for 24% (95% CI: 14-82) of the effect of household income on malaria risk, and income accounted for 11% (95% CI: 8-19) of the effect of education. Neither IRS nor bed net use was associated with malaria risk despite large, local investments in these vector control interventions. The findings testify to malaria as a disease of rural poverty and contribute further evidence to the utility of housing improvements in vector control programs.

Point-of-care p24 antigen detection for early infant diagnosis of HIV infection: cross-sectional and longitudinal studies in Zambia.

BACKGROUND: Early infant diagnosis of HIV infection is challenging in sub-Saharan Africa, particularly in rural areas, leading to delays in diagnosis and treatment. Use of a point-of-care test would overcome many challenges. This study evaluated the validity of a novel point-of-care p24 antigen detection test (LYNX) in rural and urban settings in southern Zambia. METHODS: Two studies were conducted: a cross-sectional study from 2014 to 2015 at Macha Hospital (LYNX Hospital study) and a longitudinal study from 2016 to 2018 at 12 health facilities in Southern Province, Zambia (NSEBA study). In both studies, children attending the facilities for early infant diagnosis were enrolled and a blood sample was collected for routine testing at the central lab and immediate on-site testing with the LYNX test. The performance of the LYNX test was measured in comparison to nucleic acid-based testing at the central lab. RESULTS: In the LYNX Hospital study, 210 tests were performed at a median age of 23.5 weeks (IQR: 8.9, 29.0). The sensitivity and specificity of the test were 70.0 and 100.0%, respectively. In the NSEBA study, 2608 tests were performed, including 1305 at birth and 1222 on children ≥4 weeks of age. For samples tested at birth, sensitivity was 13.6% (95% CI: 2.9, 34.9) and specificity was 99.6% (95% CI: 99.1, 99.9). While specificity was high for all ages, sensitivity increased with age and was higher for participants tested at ≥4 weeks of age (80.6%; 95% CI: 67.4, 93.7). Children with positive nucleic acid tests were more likely to be negative by the LYNX test if their mother received antiretroviral therapy during pregnancy (60.7% vs. 24.2%; p = 004). CONCLUSIONS: Considering the high specificity and moderate sensitivity that increased with age, the LYNX test could be of value for early infant diagnosis for infants ≥4 weeks of age, particularly in rural areas where centralized testing leads to long delays. Point-of-care tests with moderate sensitivity and high specificity that are affordable, easy-to-use, and easily implemented and maintained should be developed to expand access to testing and deliver same-day results to infants in areas where it is not feasible to implement nucleic acid-based point-of-care assays.

Acceptability and feasibility of testing for HIV infection at birth and linkage to care in rural and urban Zambia: a cross-sectional study.

BACKGROUND: Early infant diagnosis is important for timely identification of HIV-infected infants and linkage to care. Testing at birth has been implemented to facilitate earlier diagnosis of HIV infection but may present new challenges. This study was conducted to understand the acceptability and feasibility of birth testing in urban and rural settings in southern Zambia. METHODS: This cross-sectional study was conducted at 11 hospitals and clinics in Livingstone, Choma, and Macha in Southern Province, Zambia from 2016 to 2018. Infants born to pregnant women living with HIV at the sites were eligible for enrollment. After enrollment, a questionnaire was administered to the mother and a dried blood spot card was collected from infants for testing at a central laboratory. When results were available, mothers were notified to return to the clinic. Acceptability of birth testing was evaluated based on the proportion of women who agreed to participate and the reasons for non-participation among women who declined. Feasibility of testing at birth was evaluated using turnaround times for returning results, the proportion of women receiving results, and linkage to care for infants testing positive. RESULTS: One thousand four hundred three women were approached for the study. A small proportion declined due to refusal of birth testing (0 to 8.2% across sites). One thousand two hundred ninety women agreed to have their infants tested. The proportion of mothers receiving results ranged from 51.6 to 92.1%, and was significantly lower at the hospital than clinics in Livingstone (51.6% vs. 69.8%; p < 0.0001) and Macha (69.5% vs. 85.7%; p < 0.0001) but not Choma (85.7% vs. 92.1%; p = 0.34). For mothers who received test results, the median turnaround time from sample collection was 67 days in Livingstone and 53 days in Macha and Choma. Overall, 23 (1.8%) infants tested positive for HIV but only 8 (34.8%) were linked to care a median of 68 days (range: 29, 784) after sample collection. CONCLUSIONS: While testing at birth was acceptable, this study highlights the operational challenges under a centralized laboratory testing system. Point-of-care platforms are needed for rapid testing and return of results so HIV-infected children can be identified, linked to care, and treated as early as possible.