Appropriateness of clinical severity classification of new WHO childhood pneumonia guidance : a multi-hospital, retrospective, cohort study

Background: Management of pneumonia in many low-income and middle-income countries is based on WHO guidelines that classify children according to clinical signs that define thresholds of risk. We aimed to establish whether some children categorised as eligible for outpatient treatment might have a risk of death warranting their treatment in hospital. Methods: We did a retrospective cohort study of children aged 2–59 months admitted to one of 14 hospitals in Kenya with pneumonia between March 1, 2014, and Feb 29, 2016, before revised WHO pneumonia guidelines were adopted in the country. We modelled associations with inpatient mortality using logistic regression and calculated absolute risks of mortality for presenting clinical features among children who would, as part of revised WHO pneumonia guidelines, be eligible for outpatient treatment (non-severe pneumonia). Findings: We assessed 16 162 children who were admitted to hospital in this period. 832 (5%) of 16 031 children died. Among groups defined according to new WHO guidelines, 321 (3%) of 11 788 patients with non-severe pneumonia died compared with 488 (14%) of 3434 patients with severe pneumonia. Three characteristics were strongly associated with death of children retrospectively classified as having non-severe pneumonia: severe pallor (adjusted risk ratio 5·9, 95% CI 5·1–6·8), mild to moderate pallor (3·4, 3·0–3·8), and weight-for-age Z score (WAZ) less than −3 SD (3·8, 3·4–4·3). Additional factors that were independently associated with death were: WAZ less than −2 to −3 SD, age younger than 12 months, lower chest wall indrawing, respiratory rate of 70 breaths per min or more, female sex, admission to hospital in a malaria endemic region, moderate dehydration, and an axillary temperature of 39°C or more. Interpretation: In settings of high mortality, WAZ less than −3 SD or any degree of pallor among children with non-severe pneumonia was associated with a clinically important risk of death. Our data suggest that admission to hospital should not be denied to children with these signs and we urge clinicians to consider these risk factors in addition to WHO criteria in their decision making

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Outcomes of Children and Adolescents Admitted with Diabetic Ketoacidosis at Kenyatta National Hospital (KNH), Kenya

Background. Diabetic ketoacidosis (DKA) is an acute, major, life-threatening complication that mainly occurs in patients with type 1 diabetes mellitus and is the foremost cause of death in these children. Overall mortality in children with DKA varies from 3.4% to 13.4% in developing countries. There is a need to understand outcomes among children with DKA in sub-Saharan African countries. Objective. To determine the death rate and clinical outcomes of children and adolescents aged 0-18 years managed for DKA at Kenyatta National Hospital (KNH). Study Methods. This was a retrospective study carried out among children aged 0–18 years admitted with DKA at KNH between February 2013 and February 2018. The study site was the central records department at KNH. The inclusion criteria were children aged 0-18 years admitted with a diagnosis of DKA based on the ISPAD guidelines biochemical criteria. Results. Out of the 159 files reviewed, the median age of children was 13 years (IQR 10-15). 41.1% of patients had severe DKA while 35.7% had moderate DKA. We reported a mortality of 6.9% while 93.1% of children recovered and were discharged home. The median duration of hospital stay was 8 days. High risk of mortality was reported among children who had high serum creatinine (OR 5.8 (95% CI 1.6-21.2)), decreased urine output (OR 9.0 (95% CI 2.2-37.3)), and altered level of consciousness (OR 5.2 (95% CI 1.1-25.1)). Conclusion. DKA-associated mortality in our study was low at 6.9%. High serum creatinine, decreased urine output, and altered level of consciousness were associated with a significantly higher risk of mortality

Antiplasmodial, Cytotoxic and Acute Toxicity Activities of Vernonia lasiopus O. Hoffman

Background: Malaria continues to cause heavy morbidity and mortality and it is the fifth leading cause of death globally. The disease causes over one million deaths annually and affects many more, particularly due to increasing multi-drug resistant strains of Plasmodium falciparum. Sustained investigations in both curative and prophylactic interventions have supported the ethno-pharmacological approach to identify novel compounds as a major channel towards achieving a solution. Vernonia lasiopus has been used in traditional medicine for their antimalarial, antiviral and analgesic properties. Objective: To investigate the antiplasmodial activity and toxicity profile Vernonia lasiopus extracts. Methodology: Extraction of aerial parts and roots was done using dichloromethane:chloroform (1:1) and the resulting crude extracts each fractionated into six fractions by vacuum liquid chromatography using solvents of different polarities. The crude extract and fractions were investigated for antiplasmodial activity using the chloroquine (CQ) sensitive D6 and chloroquine (CQ) resistant W2 laboratory adapted Plasmodium falciparum strains. Cytotoxicity was evaluated on Vero 199 cells at starting concentrations of 100µg/ml, whereas acute toxicity (LD50) determined on healthy female Swiss mice (20±2 gm.). Selectivity index was used as an indicator of antiplasmodial viability. Results: The fractions of V. lasiopus roots showed higher activity combined than individually. The crude V. lasiopus root extract had an IC50 13.1 µg/ml and selectivity index >7.63. Fraction 1 of the crude root extract (VLR1) was the most viable fraction with an IC50 of 16.8 µg/ml and S.I >5.95. Both had CC50>100 µg/ml and LD50 >5000mg/kg. Conclusion: extracts of V. lasiopus aerial parts and roots were found to exhibit notable viable antiplasmodial effects, and had minimal acute toxicity in mice. Key words: Plasmodium falciparum, Vernonia lasiopus, antiplasmodial activity, toxicity, selectivity index

Combined Antibacterial and Antifungal Activities of Eucalyptus citriodora and Syzygium aromaticum Essential Oils

Background: The increasing proportion of skin infections encountered in general practice represents a substantial level of morbidity. The emergence of multi-drug resistant strains is a formidable threat to the fight against skin diseases and hence alternative forms of treatment are essential. Syzygium aromaticum and Eucalyptus citriodora oils as single entities have demonstrated potency against some of the concerned micro-organisms and any synergistic activity between the two oils could minimise development of resistance by the microorganisms to the two oils. Objective: The aim of this study was to evaluate for synergism between Eucalyptus citriodora and Syzygium aromaticum essential oils against selected pathogenic microorganisms of the skin. Materials and methods: Eucalyptus citriodora (eucalyptus oil) and Syzygium aromaticum (clove oil) essential oils were used in this study. In-vitro antimicrobial activities of Sysygium aromaticum and Eucalyptus citriodora oils, alone and in combination were tested against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa, E. coli ATCC 25922, MRSA, Candida albicans, Trichophyton mentagrophytes, Microsporum gypseum and Cryptococcus neoformans. Results: The combination of the two oils exhibited synergistic activity against Staphylococcus aureus (FICI: 0.240), E. coli (FICI: 0.54), MRSA (FICI: 0.48), and Microsporum gypseum (FICI: 0.36) while the combination exhibited additive activity against Candida albicans (FICI: 2.04). Conclusion: The combination of clove and eucalyptus oils possesses synergistic activity against most of the test pathogens and therefore may be combined for enhanced antimicrobial activity against a wide range of skin disease-causing microorganisms. Keywords: antifungal, antibacterial, synergism, Eucalyptus citriodora, Syzygium aromaticum, essential oil

Combined Antibacterial and Antifungal Activities of Eucalyptus citriodora and Syzygium aromaticum Essential Oils - Supporting Information

Background: The increasing proportion of skin infections encountered in general practice represents a substantial level of morbidity. The emergence of multi-drug resistant strains is a formidable threat to the fight against skin diseases and hence alternative forms of treatment are essential. Syzygium aromaticum and Eucalyptus citriodora oils as single entities have demonstrated potency against some of the concerned micro-organisms and any synergistic activity between the two oils could minimise development of resistance by the microorganisms to the two oils. Objective: The aim of this study was to evaluate for synergism between Eucalyptus citriodora and Syzygium aromaticum essential oils against selected pathogenic microorganisms of the skin. Materials and methods: Eucalyptus citriodora (eucalyptus oil) and Syzygium aromaticum (clove oil) essential oils were used in this study. In-vitro antimicrobial activities of Sysygium aromaticum and Eucalyptus citriodora oils, alone and in combination were tested against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa, E. coli ATCC 25922, MRSA, Candida albicans, Trichophyton mentagrophytes, Microsporum gypseum and Cryptococcus neoformans. Results: The combination of the two oils exhibited synergistic activity against Staphylococcus aureus (FICI: 0.240), E. coli (FICI: 0.54), MRSA (FICI: 0.48), and Microsporum gypseum (FICI: 0.36) while the combination exhibited additive activity against Candida albicans (FICI: 2.04). Conclusion: The combination of clove and eucalyptus oils possesses synergistic activity against most of the test pathogens and therefore may be combined for enhanced antimicrobial activity against a wide range of skin disease-causing microorganisms. Keywords: antifungal, antibacterial, synergism, Eucalyptus citriodora, Syzygium aromaticum, essential oil

Oral amoxicillin versus benzyl penicillin for severe pneumonia among kenyan children: a pragmatic randomized controlled noninferiority trial.

BACKGROUND: There are concerns that the evidence from studies showing noninferiority of oral amoxicillin to benzyl penicillin for severe pneumonia may not be generalizable to high-mortality settings. METHODS: An open-label, multicenter, randomized controlled noninferiority trial was conducted at 6 Kenyan hospitals. Eligible children aged 2-59 months were randomized to receive amoxicillin or benzyl penicillin and followed up for the primary outcome of treatment failure at 48 hours. A noninferiority margin of risk difference between amoxicillin and benzyl penicillin groups was prespecified at 7%. RESULTS: We recruited 527 children, including 302 (57.3%) with comorbidity. Treatment failure was observed in 20 of 260 (7.7%) and 21 of 261 (8.0%) of patients in the amoxicillin and benzyl penicillin arms, respectively (risk difference, -0.3% [95% confidence interval, -5.0% to 4.3%]) in per-protocol analyses. These findings were supported by the results of intention-to-treat analyses. Treatment failure by day 5 postenrollment was 11.4% and 11.0% and rising to 13.5% and 16.8% by day 14 in the amoxicillin vs benzyl penicillin groups, respectively. The most frequent cause of cumulative treatment failure at day 14 was clinical deterioration within 48 hours of enrollment (33/59 [55.9%]). Four patients died (overall mortality 0.8%) during the study, 3 of whom were allocated to the benzyl penicillin group. The presence of wheeze was independently associated with less frequent treatment failure. CONCLUSIONS: Our findings confirm noninferiority of amoxicillin to benzyl penicillin, provide estimates of risk of treatment failure in Kenya, and offer important additional evidence for policy making in sub-Saharan Africa. CLINICAL TRIAL REGISTRATION: NCT01399723