Knowledge, Attitudes, Practices, and Perceived Risk of Cervical Cancer Among Kenyan Women: Brief Report

Eastern Africa has the highest incidence and mortality rates from cervical cancer worldwide. It is important to describe the differences among women and their perceived risk of cervical cancer in order to determine target groups to increase cervical cancer screening

Sickle cell trait is not associated with endemic Burkitt lymphoma: an ethnicity and malaria endemicity-matched case-control study suggests factors controlling EBV may serve as a predictive biomarker for this pediatric cancer

Endemic Burkitt lymphoma (eBL) is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum coinfections. Malaria appears to dysregulate immunity that would otherwise control EBV, thereby contributing to eBL etiology. Juxtaposed to human genetic variants associated with protection from malaria, it has been hypothesized that such variants could decrease eBL susceptibility, historically referred to as the protective hypothesis. Past studies attempting to link sickle cell trait (HbAS), which is known to be protective against malaria, with protection from eBL were contradictory and underpowered. Therefore, using a case-control study design, we examined HbAS frequency in 306 Kenyan children diagnosed with eBL compared to 537 geographically defined and ethnically matched controls. We found 23.8% HbAS for eBL patients, which was not significantly different compared to 27.0% HbAS for controls [odds ratio (OR) = 0.85; 95% confidence interval (CI) 0.61-1.17; p-value = 0.33]. Even though cellular EBV titers, indicative of the number of latently infected B cells, were significantly higher (p-value \u3c 0.0003) in children residing in malaria holoendemic compared to hypoendemic areas, levels were not associated with HbAS genotype. Combined, this suggests that although HbAS protects against severe malaria and hyperparasitemia, it is not associated with viral control or eBL protection. However, based on receiver operating characteristic curves factors that enable the establishment of EBV persistence, in contrast to those involved in EBV lytic reactivation, may have utility as an eBL precursor biomarker. This has implications for future human genetic association studies to consider variants influencing control over EBV in addition to malaria as risk factors for eBL

Caffeine for the care of preterm infants in sub-Saharan Africa: a missed opportunity?

In 2019, 2.4 million neonates (infants <28 days of age) died globally. Of these, over 80% were preterm infants (<37 weeks gestation), with the majority born in low-income and middle-income countries.1 Complications of preterm birth, largely from respiratory distress syndrome due to surfactant deficiency, pneumonia or apnoea of prematurity (AOP), are now the leading cause of under 5 mortality globally.1 These conditions are frequently fatal in the absence of effective ventilatory support which is commonplace in neonatal units across sub-Saharan Africa. Although the global neonatal mortality rate (NMR) has halved over the past three decades, significant regional disparities remain. These correlate with World Bank and International Monetary Fund estimates of the proportion of the population living on less than US$1.90 a day, with the majority of poorer countries being in sub-Saharan Africa.1 2 As the region with the highest NMR of 27 per 1000 live births, it is estimated that a baby born in in sub-Saharan Africa is 10 times more likely to die than one born in a high income country.1 Countries in sub-Saharan Africa are unlikely to meet the global target of no more than 12 newborn deaths per 1000 live births by 2030.3 In 2017, 75 countries (almost half from sub-Saharan Africa) signed up to the ‘Every Newborn Action Plan’ that has strategic global and national actions and milestones to address gaps in maternal and newborn care.4 This ambitious commitment requires evidence-based interventions5 and innovative strategies to improve neonatal survival and longer-term outcomes

Elevated anti-Zta IgG levels and EBV viral load are associated with site of tumor presentation in endemic Burkitt's lymphoma patients: a case control study

<p>Abstract</p> <p>Background</p> <p>Endemic Burkitt's lymphoma (BL) is an extranodal tumor appearing predominantly in the jaw in younger children while abdominal tumors predominate with increasing age. Previous studies have identified elevated levels of antibodies to <it>Plasmodium falciparum </it>schizont extracts and Epstein-Barr virus (EBV) viral capsid antigens (VCA) in endemic BL relative to malaria exposed controls. However, these studies have neither determined if there were any differences based on the site of clinical presentation of the tumor nor examined a broader panel of EBV and <it>P. falciparum </it>antigens.</p> <p>Methods</p> <p>We used a suspension bead Luminex assay to measure the IgG levels against EBV antigens, VCA, EAd, EBNA-1 and Zta as well as <it>P. falciparum </it>MSP-1, LSA-1, and AMA-1 antigens in children with BL (n = 32) and in population-based age-and sex-matched controls (n = 25) from a malaria endemic region in Western Kenya with high incidence of BL. EBV viral load in plasma was determined by quantitative PCR.</p> <p>Results</p> <p>Relative to healthy controls, BL patients had significantly increased anti-Zta (<it>p </it>= 0.0017) and VCA IgG levels (<it>p </it>< 0.0001) and plasma EBV viral loads (<it>p </it>< 0.0001). In contrast, comparable IgG levels to all <it>P. falciparum </it>antigens tested were observed in BL patients compared to controls. Interestingly, when we grouped BL patients into those presenting with abdominal tumors or with jaw tumors, we observed significantly higher levels of anti-Zta IgG levels (<it>p </it>< 0.0065) and plasma EBV viral loads (<it>p </it>< 0.033) in patients with abdominal tumors compared to patients with jaw tumors.</p> <p>Conclusion</p> <p>Elevated antibodies to Zta and elevated plasma EBV viral load could be relevant biomarkers for BL and could also be used to confirm BL presenting in the abdominal region.</p

Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa

A phase III, double-blind, randomized, controlled trial (NCT00866619) in sub-Saharan Africa showed RTS,S/AS01 vaccine efficacy against malaria. We now present in-depth safety results from this study. 8922 children (enrolled at 5-17\xC2\xA0months) and 6537 infants (enrolled at 6-12\xC2\xA0weeks) were 1:1:1-randomized to receive 4 doses of RTS,S/AS01 (R3R) or non-malaria control vaccine (C3C), or 3 RTS,S/AS01 doses plus control (R3C). Aggregate safety data were reviewed by a multi-functional team. Severe malaria with Blantyre Coma Score \xE2\x89\xA42 (cerebral malaria [CM]) and gender-specific mortality were assessed post-hoc. Serious adverse event (SAE) and fatal SAE incidences throughout the study were 24.2%-28.4% and 1.5%-2.5%, respectively across groups; 0.0%-0.3% of participants reported vaccination-related SAEs. The incidence of febrile convulsions in children was higher during the first 2-3 days post-vaccination with RTS,S/AS01 than with control vaccine, consistent with the time window of post-vaccination febrile reactions in this study (mostly the day after vaccination). A statistically significant numerical imbalance was observed for meningitis cases in children (R3R: 11, R3C: 10, C3C: 1) but not in infants. CM cases were more frequent in RTS,S/AS01-vaccinated children (R3R: 19, R3C: 24, C3C: 10) but not in infants. All-cause mortality was higher in RTS,S/AS01-vaccinated versus control girls (2.4% vs 1.3%, all ages) in our setting with low overall mortality. The observed meningitis and CM signals are considered likely chance findings, that - given their severity - warrant further evaluation in phase IV studies and WHO-led pilot implementation programs to establish the RTS,S/AS01 benefit-risk profile in real-life settings

Safety and immunogenicity of the RTS,S/AS01 malaria vaccine in infants and children identified as HIV-infected during a randomized trial in sub-Saharan Africa

Background: We assessed the safety and immunogenicity of the RTS,S/AS01 malaria vaccine in a subset of children identified as HIV-infected during a large phase III randomized controlled trial conducted in seven sub-Saharan African countries. Methods: Infants 6–12 weeks and children 5–17 months old were randomized to receive 4 RTS,S/AS01 doses (R3R group), 3 RTS,S/AS01 doses plus 1 comparator vaccine dose (R3C group), or 4 comparator vaccine doses (C3C group) at study months 0, 1, 2 and 20. Infants and children with WHO stage III/IV HIV disease were excluded but HIV testing was not routinely performed on all participants; our analyses included children identified as HIV-infected based on medical history or clinical suspicion and confirmed by polymerase chain reaction or antibody testing. Serious adverse events (SAEs) and anticircumsporozoite (CS) antibodies were assessed. Results: Of 15459 children enrolled in the trial, at least 1953 were tested for HIV and 153 were confirmed as HIV-infected (R3R: 51; R3C: 54; C3C: 48). Among these children, SAEs were reported for 92.2% (95% CI: 81.1–97.8) in the R3R, 85.2% (72.9–93.4) in the R3C and 87.5% (74.8–95.3) in the C3C group over a median follow-up of 39.3, 39.4 and 38.3 months, respectively. Fifteen HIV-infected participants in each group (R3R: 29.4%, R3C: 27.8%, C3C: 31.3%) died during the study. No deaths were considered vaccinationrelated. In a matched case-control analysis, 1 month post dose 3 anti-CS geometric mean antibody concentrations were 193.3 EU/mL in RTS,S/AS01-vaccinated HIV-infected children and 491.5 EU/mL in RTS,S/ AS01-vaccinated immunogenicity controls with unknown or negative HIV status (p = 0.0001). Conclusions: The safety profile of RTS,S/AS01 in HIV-infected children was comparable to that of the comparator (meningococcal or rabies) vaccines. RTS,S/AS01 was immunogenic in HIV-infected children but antibody concentrations were lower than in children with an unknown or negative HIV status

A genomic appraisal of invasive Salmonella Typhimurium and associated antibiotic resistance in sub-Saharan Africa

Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa’s most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures

Time to full enteral feeds in hospitalised preterm and very low birth weight infants in Nigeria and Kenya

Background: Preterm (born < 37 weeks’ gestation) and very low birthweight (VLBW; <1.5kg) infants are at the greatest risk of morbidity and mortality within the first 28 days of life. Establishing full enteral feeds is a vital aspect of their clinical care. Evidence predominantly from high income countries shows that early and rapid advancement of feeds is safe and reduces length of hospital stay and adverse health outcomes. However, there are limited data on feeding practices and factors that influence the attainment of full enteral feeds among these vulnerable infants in sub-Saharan Africa. Aim: To identify factors that influence the time to full enteral feeds, defined as tolerance of 120ml/kg/day, in hospitalised preterm and VLBW infants in neonatal units in two sub-Saharan African countries. Methods: Demographic and clinical variables were collected for newborns admitted to 7 neonatal units in Nigeria and Kenya over 6-months. Multiple linear regression analysis was conducted to identify factors independently associated with time to full enteral feeds. Results: Of the 2280 newborn infants admitted, 484 were preterm and VLBW. Overall, 222/484 (45.8%) infants died with over half of the deaths (136/222; 61.7%) occurring before the first feed. The median (inter-quartile range) time to first feed was 46 (27, 72) hours of life and time to full enteral feeds (tFEF) was 8 (4.5,12) days with marked variation between neonatal units. Independent predictors of tFEF were time to first feed (unstandardised coefficient B 1.69; 95% CI 1.11 to 2.26; p value <0.001), gestational age (1.77; 0.72 to 2.81; <0.001), the occurrence of respiratory distress (-1.89; -3.50 to -0.79; <0.002) and necrotising enterocolitis (4.31; 1.00 to 7.62; <0.011). Conclusion: The use of standardised feeding guidelines may decrease variations in clinical practice, shorten tFEF and thereby improve preterm and VLBW outcomes

Prospective observational study of the challenges in diagnosing common neonatal conditions in Nigeria and Kenya

Objectives: Accurate and timely diagnosis of common neonatal conditions is crucial for reducing neonatal deaths. In low/middle-income countries with limited resources, there is sparse information on how neonatal diagnoses are made. The aim of this study was to describe the diagnostic criteria used for common conditions in neonatal units (NNUs) in Nigeria and Kenya. Design: Prospective observational study. Standard case report forms for suspected sepsis, respiratory disorders, birth asphyxia and abdominal conditions were co-developed by the Neonatal Nutrition Network (https://www.lstmed.ac.uk/nnu) collaborators. Clinicians completed forms for all admissions to their NNUs. Key data were displayed using heatmaps. Setting: Five NNUs in Nigeria and two in Kenya comprising the Neonatal Nutrition Network. Participants: 2851 neonates, which included all neonates admitted to the seven NNUs over a 6-month period. Results: 1230 (43.1%) neonates had suspected sepsis, 874 (30.6%) respiratory conditions, 587 (20.6%) birth asphyxia and 71 (2.5%) abdominal conditions. For all conditions and across all NNUs, clinical criteria were used consistently with sparse use of laboratory and radiological criteria. Conclusion: Our findings highlight the reliance on clinical criteria and extremely limited use of diagnostic technologies for common conditions in NNUs in sub-Saharan Africa. This has implications for the management of neonatal conditions which often have overlapping clinical features. Strategies for implementation of diagnostic pathways and investment in affordable and sustainable diagnostics are needed to improve care for these vulnerable infants