Papers by Lawrence Mwananyanda
Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape
Lancet Infectious Diseases, 2023
medRxiv (Cold Spring Harbor Laboratory), Aug 21, 2021
We correct common assumptions about COVID burden and disease characteristics in high-income (HIC)... more We correct common assumptions about COVID burden and disease characteristics in high-income (HIC) versus low-and middle-income (LMIC) countries by augmenting widely-used surveillance data with auxiliary data sources. We constructed an empirically-based model of serological detection rates to quantify COVID reporting rates in national and sub-national locations. From those reporting rates, we estimated relative COVID burden, finding results that contrast with estimates based on case counts and modeling. To investigate COVID mortality by age in an LMIC context, we utilized a unique morgue study of COVID in Lusaka alongside the population attributable fraction method to account for HIV comorbidity. We calculated the comorbidity-corrected age-adjusted mortality curve in Lusaka and found it significantly skewed toward younger age groups as compared to HICs. This unexpected result recommends against the unexamined use of HIC-derived parameterizations of COVID characteristics in LMIC settings, and challenges the hypothesis of an agestructure protective factor for COVID burden in Africa. Indeed, we found overall COVID burden to be higher in Lusaka than in HICs. Concurrent with high COVID burden, many LMICs have high prevalence of other public health issues such as HIV, which compete for limited health investment resources. Given differences in agestructure, comorbidities, and healthcare delivery costs, we provide a case study comparing the cost efficacy of investment in COVID versus HIV and found that even in a high HIV prevalence setting, investment in COVID remains cost-effective. As a whole, these analyses have broad implications for interpretations of COVID burden, modeling applications, and policy decision-making. COVID-19 | Surveillance | Reporting rates | Disease burden | Mortality age-structure E ffective countermeasures against the raging COVID-19 pandemic require accurate geographically-specific knowledge, but surveillance and data inequities present major challenges to these efforts. Surveillance systems are generally more robust in high-income countries (HICs), meaning that data from HICs tend to be more readily available and complete than data from low-and middle-income countries (LMICs) (1, 2). For lack of locally-specific data, epidemiological characteristics of COVID are often based on data from HICs, but the transferability to LMIC contexts remains an open question (3). Accounting for differences in surveillance and incorporating auxiliary data sources can help fill these data gaps and inform our understanding of COVID across contexts.
Clinical Infectious Diseases, Sep 1, 2021
Background. Respiratory syncytial virus (RSV) is a major cause of infant deaths. Its epidemiology... more Background. Respiratory syncytial virus (RSV) is a major cause of infant deaths. Its epidemiology in low-and middle-income countries is poorly understood. Risk factors associated with RSV-associated infant deaths that occur in community settings are incompletely known. Methods. Community deaths for infants aged 4 days to 6 months were identified during a 3-year postmortem RSV prevalence study at the main city morgue in Lusaka, Zambia, where 80% of deaths are registered. This analysis focuses on the subset of deaths for which an abbreviated verbal autopsy was available and intended to sort deaths into respiratory or nonrespiratory causes by clinical adjudication. Posterior nasopharyngeal swab samples were collected within 48 hours of death and tested for RSV using quantitative reverse-transcription polymerase chain reaction. Associations between potential risk factors were determined as relative risks with 95% confidence intervals (CIs). Results. We prospectively enrolled 798 community infant deaths with verbal autopsies and RSV laboratory results, of which 62 results were positive. The mean age of the infants was 10 weeks, and 41.4% of them were male. Of all deaths, 44% were attributed to respiratory causes. RSV was detected in 7.8% of the community infants and was significantly associated with respiratory deaths (risk ratio, 4.0 [95% CI, 2.2-7.1]). Compared with older infants, those aged 0-8 weeks had a 2.83 (95% CI, 1.30-6.15) increased risk of dying with RSV. The risk of RSV for the 0-8-week age group increased to 5.24 (1.56-33.14) with adjustment for demographics, parental education, and geography. RSV deaths were increased with domiciliary overcrowding and were concentrated in poor and dense neighborhoods in Lusaka (risk ratio, 2.00 [95% CI, 1.22-3.27]). Conclusion. RSV is a significant contributor to community respiratory deaths in this population, particularly in the first 3 months of life and in the more poor and dense parts of Lusaka.
Human Vaccines & Immunotherapeutics, Oct 10, 2018
Maternal vaccines have the potential to reduce the global burden of neonatal morbidity and mortal... more Maternal vaccines have the potential to reduce the global burden of neonatal morbidity and mortality by accessing the infant immune system before a vaccine administered in childhood would be effective. Maternal vaccines for influenza, tetanus, and pertussis have been shown to reduce neonatal disease and mortality, and other candidate vaccines for group B streptococcus and respiratory syncytial virus are being developed to continue this trend. However, safe and effective maternal vaccines will only successfully reduce neonatal illness if mothers decide to receive them. Maternal knowledge, attitudes, and beliefs around vaccines are key determinants to vaccine acceptance or vaccine hesitancy, and yet this issue is often understudied in low and middle-income country settings. A deeper understanding of these factors and how they influence maternal decision-making will allow public health practitioners and global and national policymakers to design more effective interventions. Addressing barriers to immunization at the policy and programmatic levels such as mothers' knowledge, attitudes, and beliefs of maternal vaccines is essential to increasing vaccination rates at a global scale and reducing global vaccine-preventable neonatal deaths.
PeerJ, May 11, 2023
Pediatric community-acquired pneumonia (CAP) remains a pressing global health concern, particular... more Pediatric community-acquired pneumonia (CAP) remains a pressing global health concern, particularly in low-resource settings where diagnosis and treatment rely on empiric, symptoms-based guidelines such as the WHO's Integrated Management of Childhood Illness (IMCI). This study details the delivery of IMCI-based health care to 1,320 young infants and their mothers in a low-resource urban community in Lusaka, Zambia during 2015. Our Southern Africa Mother Infant Pertussis Study (SAMIPS) prospectively monitored a cohort of mother/infant pairs across infants' first four months of life, recording symptoms of respiratory infection and antibiotics prescriptions (predominantly penicillins), and tested nasopharyngeal (NP) samples for respiratory syncytial virus (RSV) and Bordetella pertussis. Our retrospective analysis of the SAMIPS cohort found that symptoms and antibiotics use were more common in infants (43% and 15.7%) than in mothers (16.6% and 8%), while RSV and B. pertussis were observed at similar rates in infants (2.7% and 32.5%) and mothers (2% and 35.5%), albeit frequently at very low levels. In infants, we observed strong associations between symptoms, pathogen detection, and antibiotics use. Critically, we demonstrate that non-macrolide antibiotics were commonly prescribed for pertussis infections, some of which persisted across many weeks. We speculate that improved diagnostic specificity and/or clinician education paired with timely, appropriate treatment of pertussis could substantially reduce the burden of this disease while reducing the offtarget use of penicillins.
BMC Pediatrics, Sep 10, 2020
Background: Infants in the neonatal intensive care unit (NICU) are particularly susceptible to he... more Background: Infants in the neonatal intensive care unit (NICU) are particularly susceptible to healthcare-associated infections (HAIs). NICUs in low-and middle income countries face additional challenges to HAI prevention. There is a need to better understand the role of the implementation context surrounding infection prevention interventions in low-and middle income countries. Aim: The aim of this study was to identify NICU healthcare worker perceptions of an intervention to reduce bloodstream infections in a large Zambian NICU. Methods: Semi-structured interviews were conducted with NICU staff during a prospective cohort study examining the impact of an infection prevention bundle on bloodstream infections. Interviews were analyzed using an integrated approach, combining inductive theme generation with an application of the Consolidated Framework for Implementation Research (CFIR). Results: Interviews were conducted with 17 NICU staff (5 physicians and 12 nurses). Respondents believed the bundle elements were easy to use, well-designed and facilitated improved performance. Four organizational characteristics that facilitated HAI transmission were identified-(1) lack of NICU admission protocols; (2) physical crowding; (3) understaffing; and (4) equipment shortages. Respondents suggested that NICU resource constraints reflected a societal ethos that devalued the medical care of infants. Despite the challenges, respondents were highly motivated to prevent HAIs and believed this was an achievable goal. They enthusiastically welcomed the bundle but expressed serious concern about sustainability following the study. Conclusions: By eliciting healthcare worker perceptions about the context surrounding an infection prevention intervention, our study identified key organizational and societal factors to inform implementation strategies to achieve sustained improvement.
Pediatric Infectious Disease Journal, Apr 19, 2021
Background: Severity of viral respiratory illnesses can be increased with bacterial coinfection a... more Background: Severity of viral respiratory illnesses can be increased with bacterial coinfection and can vary by sex, but influence of coinfection and sex on human endemic coronavirus (CoV) species, which generally cause mild to moderate respiratory illness, is unknown. We evaluated CoV and pneumococcal co-detection by sex in childhood pneumonia. Methods: In the 2011-2014 Pneumonia Etiology Research for Child Health study, nasopharyngeal and oropharyngeal (NP/OP) swabs and other samples were collected from 3981 children <5 years hospitalized with severe or very severe pneumonia in 7 countries. Severity by NP/OP detection status of CoV (NL63, 229E, OC43 or HKU1) and high-density (≥6.9 log 10 copies/mL)
BMJ Open, Dec 1, 2020
Introduction Reliable information on rates of up-to-date coverage and timely administration of ro... more Introduction Reliable information on rates of up-to-date coverage and timely administration of routine childhood immunisations are critical for guiding public health efforts worldwide, yet prospective observation of vaccination programmes within individual communities is rare. Here, we provide a longitudinal analysis of the directly observed administration of a three-dose primary vaccination series to infants in a low-resource community in Lusaka, Zambia. Methods Throughout 2015, we recruited a longitudinal birth cohort of mother/infant pairs (initial enrolment, 1981 pairs; attending, 1497 pairs) from the periurban informal settlement of Chawama compound, located in Lusaka, Zambia. We prospectively monitored the administration of scheduled diphtheria-tetanus-pertussis (DTP) vaccinations across the first 14-18 weeks of life. We analysed study attendance and vaccine coverage, both overall and stratified by age group. We employed Kaplan-Meier analyses to estimate delays in age-appropriate administration of vaccine doses. We also assessed schedule timing violations, including early and compressed dose administration. Results At study completion, first dose (DTP1) rates were high (92.9% of attending), whereas third dose completion (DTP3) rates were far lower (61.9%). Missed vaccinations and study dropout both contributed to the low DTP3 completion rates. DTP1 was administered very late (at or after 10 weeks) to 61 infants (4.1%). DTP1 was administered too early to 64 infants (4.3%), and 77 (5.1%) received consecutive doses below the minimum recommended spacing of 28 days. Conclusions We observe substantial individual variation in the timing of early childhood DTP doses, though following this birth cohort proved challenging. Our results indicate that timely administration of both DTP1 and DTP3 remains a challenge in this community. These directlyobserved, individual-based results provide an important counterpoint to more course-grained, survey-based national and province estimates of up-to-date vaccine coverage. This study also highlights the challenges of vaccine hesitancy and suboptimal utilisation of (no-cost) healthcare services in a low-resource urban setting. ► This study provides a detailed view of a single community across a year, and may not capture longterm trends or generalise to other populations.
International Journal of Infectious Diseases, Jul 1, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Vaccine, May 1, 2018
Introduction: Severe and fatal pertussis infections are concentrated among infants who are too yo... more Introduction: Severe and fatal pertussis infections are concentrated among infants who are too young to be protected through routine vaccinations. Maternal Tdap (mTdap), which is now the standard of care in the US and UK, is considered to be the most effective way to address this gap in preventative care. Little is known about how pregnant women in low-resource settings might view mTdap. To inform strategies for mTdap implementation in these contexts, public health researchers sought to understand knowledge, attitudes, and beliefs toward pertussis and maternal vaccines and assess the barriers to vaccine acceptance. Methods: We conducted focus group discussions (FGDs) among mothers who participated in a longitudinal birth cohort study at the Chawama primary health center in Lusaka, Zambia. Since SAMIPS was not a clinical trial, but instead an observational cohort study, registration on clinicaltrials.gov was not required. Trained interviewers conducted the FGDs in January 2016 using a semi-structured interview guide, exploring participants' knowledge, attitudes and beliefs toward pertussis and vaccines. We analyzed the transcripts using Nvivo v.11 software. Results: Fifty mothers participated across 7 FGDs. Mothers had limited knowledge of pertussis and vaccines, yet expressed generally positive views of vaccinating themselves and their children. Participants conveyed very little vaccine hesitancy around maternal vaccinations, and discussed how they could protect their children's health. Mothers also highlighted barriers and facilitators to vaccine uptake, which included partner involvement, feelings of maternal authority over healthcare decision-making, and community rumors about Western medicine. Conclusion: Mothers viewed vaccinations as an important method to keep their children healthy, despite cultural myths and misconceptions about pertussis and vaccines. FGD results suggest that vaccine acceptability is high in Zambia, which is a critical factor to vaccine uptake. A strategy addressing myths and misconceptions should be prioritized if and when mTdap is introduced across low-resource settings.
Nature Communications
Reported COVID-19 cases and associated mortality remain low in many sub-Saharan countries relativ... more Reported COVID-19 cases and associated mortality remain low in many sub-Saharan countries relative to global averages, but true impact is difficult to estimate given limitations around surveillance and mortality registration. In Lusaka, Zambia, burial registration and SARS-CoV-2 prevalence data during 2020 allow estimation of excess mortality and transmission. Relative to pre-pandemic patterns, we estimate age-dependent mortality increases, totalling 3212 excess deaths (95% CrI: 2104–4591), representing an 18.5% (95% CrI: 13.0–25.2%) increase relative to pre-pandemic levels. Using a dynamical model-based inferential framework, we find that these mortality patterns and SARS-CoV-2 prevalence data are in agreement with established COVID-19 severity estimates. Our results support hypotheses that COVID-19 impact in Lusaka during 2020 was consistent with COVID-19 epidemics elsewhere, without requiring exceptional explanations for low reported figures. For more equitable decision-making du...
Etiology of Bacterial Sepsis and Isolate Resistance Patterns in Hospitalized Neonates in Zambia
Pediatric Infectious Disease Journal
Background: The Sepsis Prevention in Neonates in Zambia study is a prospective cohort study that ... more Background: The Sepsis Prevention in Neonates in Zambia study is a prospective cohort study that evaluated an infection prevention and control (IPC) bundle in the University Teaching Hospital neonatal intensive care unit (NICU) in Lusaka, Zambia. We present here the etiologies, antimicrobial resistance profiles, and associated mortality of bloodstream infections (BSI) in this cohort. Methods: Venous blood was collected from neonates with clinically suspected sepsis and cultured with an automated blood culture system. Organism identification and susceptibility testing were done using the Vitek II system. We used the CDC National Health Safety Network criteria to define pathogens and commensals. Results: There were 1120 blood cultures performed for 1060 neonates with suspected sepsis. Overall, 38% (424/1120) of cultures were positive of which 72% (306/424) grew pathogens. Blood cultures obtained after, as compared to before, 2 days of hospitalization were more likely to yield a pathog...
International Journal of Infection Control
Infection remains an important cause of maternal and newborn morbidity and mortality globally des... more Infection remains an important cause of maternal and newborn morbidity and mortality globally despite evidence that it can be reduced with adherence to infection prevention and control (IPC) practices. The implementation of IPC has been especially challenging in rural health centres. This pilot study used a non-randomised quasi-experimental design to examine the impact of a low-cost intervention bundle at five rural health facilities in Southern Province of Zambia. We used the Infection Control Assessment Tool (ICAT) and surveyed the incharge nurse, observed deliveries and reviewed logbooks to collect pre- and post-intervention data on healthcare worker IPC practices and maternal and newborn outcomes. The intervention bundle included education sessions, provision of alcohol hand rubs (AHRs), short message service (SMS) text messages and poster reminders, and monthly study visits. The overall ICAT score did not significantly increase after the intervention (64.0 vs. 71.8, maximum sco...
BMC Pregnancy and Childbirth
Background Postnatal care (PNC) is an important set of services offered to the mother and her new... more Background Postnatal care (PNC) is an important set of services offered to the mother and her newborn baby immediately after birth for the first six weeks to prevent maternal and neonatal complications and death. This qualitative study explored user and provider perspectives on quality of PNC services in the selected health facilities within the context of the Maternity Homes Access in Zambia project in the Saving Mothers Giving Life districts in rural Zambia. Methods Between October 2018 and February 2019, forty focus group discussions (FGDs) (n = 160 participants) and twelve in-depth interviews (IDIs) were conducted in four districts in Southern and Eastern provinces. FGDs comprised women who delivered within the last year, fathers, community elders, and volunteers. IDIs comprised health workers at facility, district, and provincial levels. Data were analysed using content analysis guided by the international quality of care domains derived from the World Health Organization quali...
BMC Pediatrics
Background There is very little information on the beliefs and perceptions of mothers about SIDS ... more Background There is very little information on the beliefs and perceptions of mothers about SIDS and its related risk factors in Africa. To better understand parental decisions about infant sleep practices and other risk factors for SIDS, we conducted focus group discussions (FGDs) with mothers of infants in Lusaka, Zambia. Methods FGDs involved 35 purposively sampled mothers aged 18–49 years. FGDs were conducted using a semi-structured interview guide in the local language, Nyanja. These were translated, transcribed verbatim into English, and then coded and analyzed using thematic analysis in NVivo 12. Results Six FGDs were conducted with 35 mothers in April-May 2021 across two study sites. FGD Participants were generally aware of sudden unexplained infant deaths, with several describing stories of apparent SIDS in the community. The side sleeping position was preferred and perceived to be safer for the infant with most believing the supine position posed an aspiration or choking r...
Postmortem Nasopharyngeal Microbiome Analysis of Zambian Infants With and Without Respiratory Syncytial Virus Disease: A Nested Case Control Study
Pediatric Infectious Disease Journal
Background: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and lower... more Background: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and lower respiratory tract infections in children in their first year of life, disproportionately affecting infants in developing countries. Previous studies have found that the nasopharyngeal (NP) microbiome of infants with RSV infection has specific characteristics that correlate with disease severity, including lower biodiversity, perturbations of the microbiota and differences in relative abundance. These studies have focused on infants seen in clinical or hospital settings, predominantly in developed countries. Methods: We conducted a nested case control study within a random sample of 50 deceased RSV+ infants with age at death ranging from 4 days to 6 months and 50 matched deceased RSV− infants who were all previously enrolled in the Zambia Pertussis and RSV Infant Mortality Estimation (ZPRIME) study. All infants died within the community or within 48 hours of facility admittance. As part ...
Research Square (Research Square), Jan 12, 2023
Background: There is very little information on the beliefs and perceptions of mothers about SIDS... more Background: There is very little information on the beliefs and perceptions of mothers about SIDS and its related risk factors in Africa. To better understand parental decisions about infant sleep practices and other risk factors for SIDS, we conducted focus group discussions (FGDs) with mothers of infants in Lusaka, Zambia. Methods: FGDs involved 35 purposively sampled mothers aged 18-49 years. FGDs were conducted using a semistructured interview guide in the local language, Nyanja. These were translated, transcribed verbatim into English, and then coded and analyzed using thematic analysis in NVivo 12.
medRxiv (Cold Spring Harbor Laboratory), Dec 26, 2022
Background: Respiratory Syncytial Virus (RSV) is the most common cause of bronchiolitis and lower... more Background: Respiratory Syncytial Virus (RSV) is the most common cause of bronchiolitis and lower respiratory tract infections in children in their first year of life, disproportionately affecting infants in developing countries. Previous studies have found that the nasopharyngeal microbiome of infants with RSV infection has specific characteristics that correlate with disease severity, including lower biodiversity, perturbations of the microbiota and differences in relative abundance. These studies have focused on infants seen in clinical or hospital settings, predominantly in developed countries. Methods: We conducted a nested case control study within a random sample of 50 deceased RSV+ infants with age at death ranging from 4 days to 6 months and 50 matched deceased RSV-infants who were all previously enrolled in the Zambia Pertussis and RSV Infant Mortality Estimation (ZPRIME) study. All infants died within the community or within 48 hours of facility admittance. As part of the ZPRIME study procedures, all decedents underwent one-time, post-mortem nasopharyngeal sampling. The current analysis explored the differences between the nasopharyngeal microbiome profiles of RSV+ and RSV-decedents using 16S ribosomal DNA sequencing. Results: We found that Moraxella was more abundant in the nasopharyngeal microbiome of RSV+ decedents than in RSV-decedents. Additionally, Gemella and Staphylococcus were less abundant in RSV+ decedents than in RSV-decedents. Conclusion: These results support previously reported findings of the association between the nasopharyngeal microbiome and RSV and suggest that changes in the abundance of these microbes are likely specific to RSV and may correlate with mortality associated with the disease. .
Gates Open Research, 2021
Background Accurate patient identification is essential for delivering longitudinal care. Our tea... more Background Accurate patient identification is essential for delivering longitudinal care. Our team developed an ear biometric system (SEARCH) to improve patient identification. To address how ear growth affects matching rates longitudinally, we constructed an infant cohort, obtaining ear image sets monthly to map a 9-month span of observations. This analysis had three main objectives: 1) map trajectory of ear growth during the first 9 months of life; 2) determine the impact of ear growth on matching accuracy; and 3) explore computer vision techniques to counter a loss of accuracy. Methodology Infants were enrolled from an urban clinic in Lusaka, Zambia. Roughly half were enrolled at their first vaccination visit and ~half at their last vaccination. Follow-up visits for each patient occurred monthly for 6 months. At each visit, we collected four images of the infant’s ears, and the child’s weight. We analyze ear area versus age and change in ear area versus age. We conduct pair-wis...
Journal of the Pediatric Infectious Diseases Society, 2021
Background Most pediatric HIV cases in Africa reflect maternal to child transmission (MTCT). The ... more Background Most pediatric HIV cases in Africa reflect maternal to child transmission (MTCT). The persistently high seroprevalence of HIV in pregnant women (16.6%) and the low rates of mother to child HIV transmission (~2%) have resulted in a high number of children who are HIV exposed but uninfected (HEU). HIV exposed but uninfected (HEU) children have increased rates of morbidity and mortality vs. HIV unexposed and uninfected (HUU). Methods To explore the mechanisms behind this phenomenon, each case and control was sampled using a nasopharyngeal NP swab and an oropharyngeal (OP). A multiplex real-time polymerase chain reaction (PCR) assay was used to determine the presence of Streptococcus pneumoniae and Pneumocystis jirovecii in the NP/OP specimens. We compared nasopharyngeal carriage rates of S. pneumoniae and P. jirovecii between HIV-infected, HEU, or HUU case (pneumonia) and control (without pneumonia) children. In bivariate analyses, using carriage as a dichotomous outcome, pr...
Uploads
Papers by Lawrence Mwananyanda