Components of clean delivery kits and newborn mortality in the Zambia Chlorhexidine Application Trial (ZamCAT): An observational study.

BACKGROUND: Neonatal infection, a leading cause of neonatal death in low- and middle-income countries, is often caused by pathogens acquired during childbirth. Clean delivery kits (CDKs) have shown efficacy in reducing infection-related perinatal and neonatal mortality. However, there remain gaps in our current knowledge, including the effect of individual components, the timeline of protection, and the benefit of CDKs in home and facility deliveries. METHODS AND FINDINGS: A post hoc secondary analysis was performed using nonrandomized data from the Zambia Chlorhexidine Application Trial (ZamCAT), a community-based, cluster-randomized controlled trial of chlorhexidine umbilical cord care in Southern Province of Zambia from February 2011 to January 2013. CDKs, containing soap, gloves, cord clamps, plastic sheet, razor blade, matches, and candle, were provided to all pregnant women. Field monitors made a home-based visit to each participant 4 days postpartum, during which CDK use and newborn outcomes were ascertained. Logistic regression was used to study the association between different CDK components and neonatal mortality rate (NMR). Of 38,579 deliveries recorded during the study, 36,996 newborns were analyzed after excluding stillbirths and those with missing information. Gloves, cord clamps, and plastic sheets were the most frequently used CDK item combination in both home and facility deliveries. Each of the 7 CDK components was associated with lower NMR in users versus nonusers. Adjusted logistic regression showed that use of gloves (odds ratio [OR] 0.33, 95% CI 0.24-0.46), cord clamp (OR 0.51, 95% CI 0.38-0.68), plastic sheet (OR 0.46, 95% CI 0.34-0.63), and razor blade (OR 0.69, 95% CI 0.53-0.89) were associated with lower risk of newborn mortality. Use of gloves and cord clamp were associated with reduced risk of immediate newborn death (<24 hours). Reduction in risk of early newborn death (1-6 days) was associated with use of gloves, cord clamps, plastic sheets, and razor blades. In examining perinatal mortality (stillbirth plus neonatal death in the first 7 days of life), similar patterns were observed. There was no significant reduction in risk of late newborn mortality (7-28 days) with CDK use. Study limitations included potential recall bias of CDK use and inability to establish causality, as this was a secondary observational study. CONCLUSIONS: CDK use was associated with reductions in early newborn mortality at both home and facility deliveries, especially when certain kit components were used. While causality could not be established in this nonrandomized secondary analysis, given these beneficial associations, scaling up the use of CDKs in rural areas of sub-Saharan Africa may improve neonatal outcomes. TRIAL REGISTRATION: Name of trial: Zambia Chlorhexidine Application Trial (ZamCAT) Name of registry: Clinicaltrials.gov Trial number: NCT01241318.

Multisystem Inflammatory Syndrome in an Adult With COVID-19-A Trial of Anakinra: A Case Report.

COVID-19 disease has been a pandemic caused by a ß-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A life-threatening multisystem inflammatory syndrome (MIS), secondary to SARS-CoV-2 virus infection, sharing common features with Kawasaki disease shock syndrome, staphylococcal/streptococcal shock syndrome, and macrophage activation syndrome in pediatric patients has been described. A total of 27 cases in adults (MIS-A) with a similar presentation have been reported so far. Here we describe the case of a 21-year-old man admitted with abdominal pain, diarrhea, tachycardia, and low blood pressure. He had elevated troponin, ferritin, and interleukin-2 receptor levels and had evidence of myocarditis. He tested positive for SARS-CoV-2 IgG antibody, and a diagnosis of MIS-A was made. Our case adds to the scant literature on this topic, and to our knowledge, it is the first case where anakinra was administered. He recovered well. MIS-A should be considered when young adults present with multiorgan dysfunction.

Can community health workers identify omphalitis? A validation study from Southern Province, Zambia.

OBJECTIVE: Omphalitis, or umbilical cord infection, is an important cause of newborn morbidity and mortality in low-resource settings. We tested an algorithm that task-shifts omphalitis diagnosis to community-level workers in sub-Saharan Africa. METHODS: Community-based field monitors and Zambian paediatricians independently evaluated newborns presenting to health facilities in Southern Zambia using a signs and symptoms checklist. Responses were compared against the paediatrician's gold standard clinical diagnosis. RESULTS: Of 1009 newborns enrolled, 6.2% presented with omphalitis per the gold standard clinical diagnosis. Paediatricians' signs and symptoms with the highest sensitivity were presence of pus (79.4%), redness at the base (50.8%) and newborn flinching when cord was palpated (33.3%). The field monitor's signs and symptoms answers had low correlation with paediatrician's answers; all signs and symptoms assessed had sensitivity <16%. CONCLUSION: Despite extensive training, field monitors could not consistently identify signs and symptoms associated with omphalitis in the sub-Saharan African setting.

Single-test syphilis serology: A case of not seeing the forest for the trees.

INTRODUCTION: There have been few empirical studies for diagnostic test accuracy of syphilis using a sequence of rapid tests in populations with low prevalence of syphilis such as pregnant women. This analysis describes syphilis test positivity frequency among pregnant women at an antenatal clinic in Zambia using a reverse-sequence testing algorithm for antenatal syphilis screening. METHODS: Between August 2019 and May 2023, we recruited 1510 pregnant women from a peri-urban hospital in Lusaka, Zambia. HIV positive and HIV negative women were enrolled in a 1:1 ratio. Blood collected at recruitment from the pregnant mothers was tested on-site for syphilis using a rapid treponemal test. Samples that tested positive were further tested at a different laboratory, with rapid plasma reagin using archived plasma. RESULTS: Of the total 1,421 sera samples which were screened with a rapid treponemal test, 127 (8.9%) were positive and 1,294 (91.1%) were negative. Sufficient additional samples were available to perform RPR testing on 114 of the 127 (89.8%) RDT positive specimens. Thirty-one (27.2%) of these 114 were reactive by RPR and 83 (72.8%) were negative, resulting in a syphilis overtreatment rate of 3 fold (i.e, 84/114). Insufficient sample or test kit availability prevented any testing for the remaining 89 (5.9%) participants. CONCLUSION: Use of only treponemal tests in low prevalence populations, like pregnant women, subjects individuals with non-active syphilis to the costs and possible risks of overtreatment. The use of the dual treponemal and non-treponemal tests would minimize this risk at some additional cost.

Preterm birth among women with HIV: impact of preconception cART initiation.

OBJECTIVE: To examine the risk of preterm birth (PTB) and small for gestational age (SGA) among women with HIV compared to women without HIV. Secondary objectives were to explore the role of maternal immune activation (IA) and effect of cART timing on these outcomes. DESIGN: Prospective observational cohort. SETTING: Urban government-run clinic at Chawama Hospital in Lusaka, Zambia. PARTICIPANTS: A total of 1481 women with and without HIV with singleton pregnancies enrolled before 26 weeks' gestation by ultrasound dating. METHODS: From August 2019 to November 2022, pregnant women were enrolled in a 1 : 1 ratio of HIV infection. Maternal baseline clinical factors were collected, as well as CD4 + , viral load and CD8 + T-cell IA in women with HIV. Birth outcomes were also collected. The association of HIV-exposure and cART timing on outcomes was assessed by multivariable logistic regression. The independent role of IA was determined by mediation analysis. MAIN OUTCOME MEASURES: PTB (<37 weeks) and SGA. RESULTS: There were 38 fetal deaths and 1230 singleton live births. Maternal HIV infection was associated with PTB [adjusted odds ratio (AOR) 1.60, 95% confidence interval (CI) 1.11-2.32] and to a lesser extent SGA (AOR 1.29, 95% CI 0.98-1.70). Maternal cART timing impacted these associations, with highest risk in women who started cART after conception (PTB AOR 1.77, 95% CI 1.09-2.87, SGA AOR 1.52, 95% CI 1.04-2.22). Maternal IA was not associated with PTB independent of HIV infection. CONCLUSIONS: HIV is associated with PTB. Risk of PTB and SGA was highest in women with HIV who started cART in pregnancy, a modifiable risk factor.

Impact of beliefs on perception of newborn illness, caregiver behaviors, and care-seeking practices in Zambia's Southern province.

Despite reductions in the number of under-five deaths since the release of the Sustainable Development Goals, the proportion of neonatal deaths among all under-five deaths has remained high. Neonatal health is linked to newborn care practices which are tied to distinct cultural perceptions of health and illness. We assessed how community beliefs in Zambia's Southern Province influence newborn care behaviors, perception of illness, and care-seeking practices, using qualitative data collected between February and April 2010. A total of 339 women participated in 36 focus group discussions (FGDs), with 9 FGDs conducted in each of the four study districts. In addition, 42 in-depth interviews (IDIs) were conducted with various key informants, with 11 IDIs conducted in Choma, 11 IDIs in Monze, 10 IDIs in Livingstone, and 10 IDIs in Mazabuka. The FGDs and IDIs indicate that beliefs among the Tonga people regarding postnatal illness prevention and management influence perceptions of newborn illness and care-seeking practices. Care seeking behaviors including when, why, and where parents seek newborn care are intimately tied to perception of disease among the Tonga people. These beliefs may stem from both indigenous and Western perspectives in Zambia's Southern Province. Findings are consistent with other analyses from Southern Province that highlighted the benefit of integrating local practices with Western biomedical care. Health systems models, led by policy makers and program designers, could aim to find synergies between community practices and formal health systems to support positive behavior change and satisfy multiple stakeholders.

Global health training for pediatric residents.

The FOPO Global Health Working Group concludes that global health experiences are important for pediatric residency training and offers five recommendations: 1) There is a need to articulate clearly the rationale supporting the creation of global health experiences in pediatric residency programs. 2) A core curriculum needs to be established for a consistent and meaningful educational experience. The curriculum should include the underlying principles discussed above and should engage representatives from potential host countries in the development of the curriculum. 3) Promoting the opportunity for a global health experience in all residency programs will require a collaborative effort across programs, perhaps at the national level through the Association of Pediatric Program Directors or through the already established Global Health Education Consortium (GHEC).34 A clearinghouse for curricula and for host organizations/institutions both abroad and within the United States and Canada should be established. 4) Global health training needs to be studied rigorously, and lessons learned should be shared. 5) Pediatric residency programs should respect the rights, autonomy, and confidentiality of patients and families in clinical care, research, and operational programs. The FOPO Global Health Working Group looks forward to serving as a focal point to promote discussion on this important issue to the health of our world's children.

Influence of newborn health messages on care-seeking practices and community health behaviors among participants in the Zambia Chlorhexidine Application Trial.

BACKGROUND: Identifying and understanding traditional perceptions that influence newborn care practices and care-seeking behavior are crucial to developing sustainable interventions to improve neonatal health. The Zambia Chlorhexidine Application Trial (ZamCAT), a large-scale cluster randomized trial, assessed the impact of 4% chlorhexidine on neonatal mortality and omphalitis in Southern Province, Zambia. The main purpose of this post-ZamCAT qualitative study was to understand the impact of newborn care health messages on care-seeking behavior for neonates and the acceptability, knowledge, and attitudes towards chlorhexidine cord care among community members and health workers in Southern Province. METHODS & FINDINGS: Five focus group discussions and twenty-six in-depth interviews were conducted with mothers and health workers from ten health centers (5 rural and 5 peri-urban/urban). Community perceptions and local realities were identified as fundamental to care-seeking decisions and influenced individual participation in particular health-seeking behaviors. ZamCAT field monitors (data collectors) disseminated health messages at the time of recruitment at the health center and during subsequent home visits. Mothers noted that ZamCAT field monitors were effective in providing lessons and education on newborn care practices and participating mothers were able to share these messages with others in their communities. Although the study found no effect of chlorhexidine cord washes on neonatal mortality, community members had positive views towards chlorhexidine as they perceived that it reduced umbilical cord infections and was a beneficial alternative to traditional cord applications. CONCLUSION: The acceptability of health initiatives, such as chlorhexidine cord application, in community settings, is dependent on community education, understanding, and engagement. Community-based approaches, such as using community-based cadres of health workers to strengthen referrals, are an acceptable and potentially effective strategy to improve care-seeking behaviors and practices.

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.

Implementation and Operational Research: Integration of PMTCT and Antenatal Services Improves Combination Antiretroviral Therapy Uptake for HIV-Positive Pregnant Women in Southern Zambia: A Prototype for Option B+?

BACKGROUND: Early initiation of combination antiretroviral therapy (cART) for HIV-positive pregnant women can decrease vertical transmission to less than 5%. Programmatic barriers to early cART include decentralized care, disease-stage assessment delays, and loss to follow-up. INTERVENTION: Our intervention had 3 components: integrated HIV and antenatal services in 1 location with 1 provider, laboratory courier to expedite CD4 counts, and community-based follow-up of women-infant pairs to improve prevention of mother-to-child transmission attendance. Preintervention HIV-positive pregnant women were referred to HIV clinics for disease-stage assessment and cART initiation for advanced disease (CD4 count <350 cells/µL or WHO stage >2). METHODS: We used a quasi-experimental design with preintervention/postintervention evaluations at 6 government antenatal clinics (ANCs) in Southern Province, Zambia. Retrospective clinical data were collected from clinic registers during a 7-month baseline period. Postintervention data were collected from all antiretroviral therapy-naive, HIV-positive pregnant women and their infants presenting to ANC from December 2011 to June 2013. RESULTS: Data from 510 baseline women-infant pairs were analyzed and 624 pregnant women were enrolled during the intervention period. The proportion of HIV-positive pregnant women receiving CD4 counts increased from 50.6% to 77.2% [relative risk (RR) = 1.81; 95% confidence interval (CI): 1.57 to 2.08; P < 0.01]. The proportion of cART-eligible pregnant women initiated on cART increased from 27.5% to 71.5% (RR = 2.25; 95% CI: 1.78 to 2.83; P < 0.01). The proportion of eligible HIV-exposed infants with documented 6-week HIV PCR test increased from 41.9% to 55.8% (RR = 1.33; 95% CI: 1.18 to 1.51; P < 0.01). CONCLUSIONS: Integration of HIV care into ANC and community-based support improved uptake of CD4 counts, proportion of cART-eligible women initiated on cART, and infants tested.

Assessment of the impact of rapid syphilis tests on syphilis screening and treatment of pregnant women in Zambia.

OBJECTIVE: To evaluate the impact of rapid syphilis tests (RSTs) on syphilis testing and treatment in pregnant women in Kalomo District, Zambia. METHODS: In March 2012, health workers at all 35 health facilities in Kalomo Distract were trained in RST use and penicillin treatment. In March 2013, data were retrospectively abstracted from 18 randomly selected health facilities and stratified into three time intervals: baseline (6months prior to RST introduction), midline (0-6 months after RST introduction), and endline (7-12 months after RST introduction). RESULTS: Data collected on 4154 pregnant women showed a syphilis-reactive seroprevalence of 2.7%. The proportion of women screened improved from baseline (140/1365, 10.6%) to midline (976/1446, 67.5%), finally decreasing at endline (752/1337, 56.3%) (P<0.001). There was no significant difference in the proportion of syphilis-seroreactive pregnant women who received 1 dose of penicillin before (1/2, 50%) or after (5/48, 10.4%; P=0.199) RST introduction with low treatment rates throughout. CONCLUSION: With RST scale-up in Zambia and other resource-limited settings, same-day test and treatment with penicillin should be prioritized to achieve the goal of eliminating congenital syphilis.

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.

Local perceptions, cultural beliefs and practices that shape umbilical cord care: a qualitative study in Southern Province, Zambia.

BACKGROUND: Global policy regarding optimal umbilical cord care to prevent neonatal illness is an active discussion among researchers and policy makers. In preparation for a large cluster-randomized control trial to measure the impact of 4% chlorhexidine as an umbilical wash versus dry cord care on neonatal mortality in Southern Province, Zambia, we performed a qualitative study to determine local perceptions of cord health and illness and the cultural belief system that shapes umbilical cord care knowledge, attitudes, and practices. METHODS AND FINDINGS: This study consisted of 36 focus group discussions with breastfeeding mothers, grandmothers, and traditional birth attendants, and 42 in-depth interviews with key community informants. Semi-structured field guides were used to lead discussions and interviews at urban and rural sites. A wide variation in knowledge, beliefs, and practices surrounding cord care was discovered. For home deliveries, cords were cut with non-sterile razor blades or local grass. Cord applications included drying agents (e.g., charcoal, baby powder, dust), lubricating agents (e.g., Vaseline, cooking oil, used motor oil) and agents intended for medicinal/protective purposes (e.g., breast milk, cow dung, chicken feces). Concerns regarding the length of time until cord detachment were universally expressed. Blood clots in the umbilical cord, bulongo-longo, were perceived to foreshadow neonatal illness. Management of bulongo-longo or infected umbilical cords included multiple traditional remedies and treatment at government health centers. CONCLUSION: Umbilical cord care practices and beliefs were diverse. Dry cord care, as recommended by the World Health Organization at the time of the study, is not widely practiced in Southern Province, Zambia. A cultural health systems model that depicts all stakeholders is proposed as an approach for policy makers and program implementers to work synergistically with existing cultural beliefs and practices in order to maximize effectiveness of evidence-based interventions.

Developing a Career in Global Health: Considerations for Physicians-in-Training and Academic Mentors.

BACKGROUND: Global health is an expansive field, and global health careers are as diverse as the practice of medicine, with new paths being forged every year. Interest in global health among medical students, residents, and fellows has never been higher. As a result, a greater number of these physicians-in-training are participating in global health electives during their training. However, there is a gap between the level of trainee interest and the breadth and depth of educational opportunities that prepare them for a career in global health. OBJECTIVE: Global health experiences can complement and enhance each step of traditional physician training, from medical school through residency and fellowship. Global health experiences can expose trainees to patients with diverse pathologies, improve physical exam skills by decreasing reliance on laboratory tests and imaging, enhance awareness of costs and resource allocation in resource-poor settings, and foster cultural sensitivity. The aim of this article is to describe issues faced by physicians-in-training and the faculty who mentor them as trainees pursue careers in global health. METHODS: We conducted a narrative review that addresses opportunities and challenges, competing demands on learners' educational schedules, and the need for professional development for faculty mentors. CONCLUSIONS: A widening gap between trainee interest and the available educational opportunities in global health may result in many medical students and residents participating in global health experiences without adequate preparation and mentorship. Without this essential support, global health training experiences may have detrimental consequences on both trainees and the communities hosting them. We discuss considerations at each training level, options for additional training, current career models in global health, and challenges and potential solutions during training and early career development.