Novel treatment strategies for chronic kidney disease: insights from the animal kingdom

Many of the >2 million animal species that inhabit Earth have developed survival mechanisms that aid in the prevention of obesity, kidney disease, starvation, dehydration and vascular ageing; however, some animals remain susceptible to these complications. Domestic and captive wild felids, for example, show susceptibility to chronic kidney disease (CKD), potentially linked to the high protein intake of these animals. By contrast, naked mole rats are a model of longevity and are protected from extreme environmental conditions through mechanisms that provide resistance to oxidative stress. Biomimetic studies suggest that the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) offers protection in extreme environmental conditions and promotes longevity in the animal kingdom. Similarly, during months of fasting, immobilization and anuria, hibernating bears are protected from muscle wasting, azotaemia, thrombotic complications, organ damage and osteoporosis - features that are often associated with CKD. Improved understanding of the susceptibility and protective mechanisms of these animals and others could provide insights into novel strategies to prevent and treat several human diseases, such as CKD and ageing-associated complications. An integrated collaboration between nephrologists and experts from other fields, such as veterinarians, zoologists, biologists, anthropologists and ecologists, could introduce a novel approach for improving human health and help nephrologists to find novel treatment strategies for CKD

Respiratory microbiota and lower respiratory tract disease

INTRODUCTION: The respiratory airways harbor a complex succession of ecological niches with distinct but related bacterial communities. Particular challenges of respiratory microbiome research have led to limited scientific output compared to other human microbiomes. Areas covered: In this review, we summarize the current state of knowledge of the bacterial respiratory microbiome, with a particular focus on associations between the respiratory microbiome and lower respiratory tract conditions. Expert commentary: There is growing evidence that the respiratory microbiome is associated with lower respiratory infectious diseases and related conditions. Most respiratory microbiome reports are metataxonomic cross-sectional or case-control studies with relatively small sample sizes. Large, prospective projects with metatranscriptomics or metabolomics approach are needed to unravel the effect of the respiratory microbiome on health-related conditions. Moreover, standardization in sampling, library preparation, sequencing techniques and data analysis should be encouraged

Hypoxaemia in Mozambican children < 5 years of age admitted to hospital with clinical severe pneumonia: clinical features and performance of predictor models

OBJECTIVE: To determine the prevalence of hypoxaemia among under-five children admitted to hospital with clinical severe pneumonia, and to assess the performance to diagnose hypoxaemia of models based on clinical signs. METHODS: We conducted a hospital-based survey in a district hospital from Southern Mozambique. RESULTS: A total of 825 children were recruited after obtaining an informed consent. The prevalence of hypoxaemia on admission was 27.9%, and 19.8% of these children died (OR compared to non-hypoxaemic children 3.22, 95%CI 1.98 - 5.21, p<0.001). The model with larger area under the ROC curve (AUC-ROC) to predict hypoxaemia included cyanosis or thoracoabdominal breathing or respiratory rate >/= 70 breaths per minute. None of the models performed well when tested in different case scenarios of oxygen availability through mathematical modelling, with over 50% of hypoxaemic children not receiving oxygen even in favourable case scenarios. CONCLUSIONS: Clinical signs alone or in combination are not suitable to diagnose hypoxaemia. The use of pulse oximeters should be strongly encouraged. This article is protected by copyright. All rights reserved

Strengthening Health Systems and Improving the Capacity of Pediatric Care Centers to Respond to Epidemics Such as COVID-19 in Resource-limited Settings

The coronavirus disease-2019 (COVID-19) pandemic has highlighted in dramatic fashion the weaknesses of health systems worldwide in responding to emerging pandemics [1]. Although many governments, nongovernment organizations (NGOs) and multinational organizations like the World Health Organization (WHO) have prioritized the strengthening of health systems, and developed pandemic preparedness plans, the world’s uneven (and often belated) response to the COVID-19 pandemic suggests that many of these plans were insufficient and that the global health community will need to improve resource allocation, information-sharing and government coordination in order to minimize the impact of future outbreaks [2]. We are particularly concerned that existing preparedness plans do not adequately address the special needs of children; the relatively low hospitalization and death rates of children in the COVID-19 pandemic may result in the continuation of those needs being overlooked [3]. Additionally, the needs of children in low-resource settings, which differ in many ways from those of wealthier settings, may be even further at stake. As health systems begin to reassess their preparedness plans, this pandemic gives the world the opportunity to put safety measures in place to protect children now, and in turn to prepare for future outbreaks that will, sooner or later, affect children to a greater degree than this pandemic has thus far

Hypoglycemia and Risk Factors for Death in 13 Years of Pediatric Admissions in Mozambique

Hypoglycemia is a life-threatening complication of several diseases in childhood. We describe the prevalence and incidence of hypoglycemia among admitted Mozambican children, establishing its associated risk factors. We retrospectively reviewed clinical data of 13 years collected through an ongoing systematic morbidity surveillance in Manhica District Hospital in rural Mozambique. Logistic regression was used to identify risk factors for hypoglycemia and death. Minimum community-based incidence rates (MCBIRs) for hypoglycemia were calculated using data from the demographic surveillance system. Of 49,089 children < 15 years hospitalized in Manhica District Hospital, 45,573 (92.8%) had a glycemia assessment on admission. A total of 1,478 children (3.2%) presented hypoglycemia (< 3 mmol/L), of which about two-thirds (972) were with levels < 2.5 mmol/L. Independent risk factors for hypoglycemia on admission and death among hypoglycemic children included prostration, unconsciousness, edema, malnutrition, and bacteremia. Hypoglycemic children were significantly more likely to die (odds ratio [OR] = 7.11; P < 0.001), with an associated case fatality rate (CFR) of 19.3% (245/1,267). Overall MCBIR of hypoglycemia was 1.57 episodes/1,000 child years at risk (CYAR), significantly decreasing throughout the study period. Newborns showed the highest incidences (9.47 episodes/1,000 CYAR, P < 0.001). Hypoglycemia remains a hazardous condition for African children. Symptoms and signs associated to hypoglycemia should trigger the verification of glycemia and the implementation of life-saving corrective measures

Climate change and the kidney

The worldwide increase in temperature has resulted in a marked increase in heat waves (heat extremes) that carries a markedly increased risk for morbidity and mortality. The kidney has a unique role not only in protecting the host from heat and dehydration but also is an important site of heat-associated disease. Here we review the potential impact of global warming and heat extremes on kidney diseases. High temperatures can result in increased core temperatures, dehydration, and blood hyperosmolality. Heatstroke (both clinical and subclinical whole-body hyperthermia) may have a major role in causing both acute kidney disease, leading to increased risk of acute kidney injury from rhabdomyolysis, or heat-induced inflammatory injury to the kidney. Recurrent heat and dehydration can result in chronic kidney disease (CKD) in animals and theoretically plays a role in epidemics of CKD developing in hot regions of the world where workers are exposed to extreme heat. Heat stress and dehydration also has a role in kidney stone formation, and poor hydration habits may increase the risk for recurrent urinary tract infections. The resultant social and economic consequences include disability and loss of productivity and employment. Given the rise in world temperatures, there is a major need to better understand how heat stress can induce kidney disease, how best to provide adequate hydration, and ways to reduce the negative effects of chronic heat exposure.Published versio

Detection of Streptococcus pneumoniae and Haemophilus influenzae type B by real-time PCR from dried blood spot samples among children with pneumonia: a useful approach for developing countries

Correction https://doi.org/10.1371/journal.pone.0147678Background: Dried blood spot (DBS) is a reliable blood collection method for storing samples at room temperature and easily transporting them. We have previously validated a Real-Time PCR for detection of Streptococcus pneumoniae in DBS. The objective of this study was to apply this methodology for the diagnosis of S. pneumoniae and Haemophilus influenzae b (Hib) in DBS samples of children with pneumonia admitted to two hospitals in Mozambique and Morocco. Methods: Ply and wzg genes of S. pneumoniae and bexA gene of Hib, were used as targets of Real-Time PCR. 329 DBS samples of children hospitalized with clinical diagnosis of pneumonia were tested. Results: Real-Time PCR in DBS allowed for a significant increase in microbiological diagnosis of S. pneumoniae and Hib. When performing blood bacterial culture, only ten isolates of S. pneumoniae and none of Hib were detected (3·0% positivity rate, IC95% 1·4-5·5%). Real-Time PCR from DBS samples increased the detection yield by 4x fold, as 30 S. pneumoniae and 11 Hib cases were detected (12·4% positivity rate, IC95% 9·0-16·5%; P<0·001). Conclusion: Real-Time PCR applied in DBS may be a valuable tool for improving diagnosis and surveillance of pneumonia caused by S. pneumoniae or Hib in developing countries

Oral polio revaccination is associated with changes in gut and upper respiratory microbiomes of infants

Copyright © 2022 Medeiros, Ingham, Nanque, Correia, Stegger, Andersen, Fisker, Benn, Lanaspa, Silveira and Abrantes.After the eradication of polio infection, the plan is to phase-out the live-attenuated oral polio vaccine (OPV). Considering the protective non-specific effects (NSE) of OPV on unrelated pathogens, the withdrawal may impact child health negatively. Within a cluster-randomized trial, we carried out 16S rRNA deep sequencing analysis of fecal and nasopharyngeal microbial content of Bissau-Guinean infants aged 4-8 months, before and after 2 months of OPV revaccination (revaccinated infants = 47) vs. no OPV revaccination (control infants = 47). The aim was to address changes in the gut and upper respiratory bacterial microbiotas due to revaccination. Alpha-diversity for both microbiotas increased similarly over time in OPV-revaccinated infants and controls, whereas greater changes over time in the bacterial composition of gut ( p adjusted < 0.001) and upper respiratory microbiotas ( p adjusted = 0.018) were observed in the former. Taxonomic analysis of gut bacterial microbiota revealed a decrease over time in the median proportion of Bifidobacterium longum for all infants (25-14.3%, p = 0.0006 in OPV-revaccinated infants and 25.3-11.6%, p = 0.01 in controls), compatible with the reported weaning. Also, it showed a restricted increase in the median proportion of Prevotella_9 genus in controls (1.4-7.1%, p = 0.02), whereas in OPV revaccinated infants an increase over time in Prevotellaceae family (7.2-17.4%, p = 0.005) together with a reduction in median proportion of potentially pathogenic/opportunistic genera such as Escherichia/ Shigella (5.8-3.4%, p = 0.01) were observed. Taxonomic analysis of upper respiratory bacterial microbiota revealed an increase over time in median proportions of potentially pathogenic/opportunistic genera in controls, such as Streptococcus (2.9-11.8%, p = 0.001 and Hemophilus (11.3-20.5%, p = 0.03), not observed in OPV revaccinated infants. In conclusion, OPV revaccination was associated with a healthier microbiome composition 2 months after revaccination, based on a more abundant and diversified bacterial community of Prevotellaceae and fewer pathogenic/opportunistic organisms. Further information on species-level differentiation and functional analysis of microbiome content are warranted to elucidate the impact of OPV-associated changes in bacterial microbiota on child health.publishersversionpublishe

Under treatment of pneumonia among children under 5 years of age in a malaria-endemic area: population-based surveillance study conducted in Manhica district- rural, Mozambique

BACKGROUND: Integrated Management of Childhood Illness (IMCI) guidelines were developed to decrease morbidity and mortality, yet implementation varies across settings. Factors associated with poor adherence are not well understood. METHODS: We used data from Manhica District Hospital outpatient department and five peripheral health centers to examine pneumonia management for children <5 years old from January 2008 to June 2011. Episodes of IMCI-defined pneumonia (cough or difficult breathing plus tachypnea), severe pneumonia (pneumonia plus chest wall in-drawing), and/or clinician-diagnosed pneumonia (based on discharge diagnosis) were included. RESULTS: Among severe pneumonia episodes, 96.2% (2,918/3,032) attended in the outpatient department and 70.0% (291/416) attended in health centers were appropriately referred to the emergency department. Age<1 year, malnutrition and various physical exam findings were associated with referral. For non-severe pneumonia episodes, antibiotics were prescribed in 45.7% (16,094/35,224). Factors associated with antibiotic prescription included age <1 year, abnormal auscultatory findings, and clinical diagnosis of pneumonia; diagnosis of malaria or gastroenteritis and pallor were negatively associated with antibiotic prescription. CONCLUSION: Adherence to recommended management of severe pneumonia was high in a hospital outpatient department, but suboptimal in health centers. Antibiotics were prescribed in fewer than half of non-severe pneumonia episodes, and diagnosis of malaria was the strongest risk factor for incorrect management

High prevalence of Pneumocystis jirovecii pneumonia among Mozambican children < 5 years of age admitted to hospital with clinical severe pneumonia

We aimed to describe Pneumocystis jirovecii pneumonia (PCP) prevalence and features in children from sub-Saharan Africa, and to investigate PCP-associated risk factors. During 2006-2007 we used molecular methods to test children younger than 5 years old admitted with severe pneumonia to a hospital in Southern Mozambique for Pneumocystis infection. We recruited 834 children. PCP prevalence was 6.8% and HIV prevalence was 25.7%. The in-hospital and delayed mortality were significantly higher among children with PCP (20.8% vs. 10.2 %, p=0.021, and 11.5% vs. 3.6%, p=0.044, respectively). Clinical features were mostly overlapping between the two groups. Independent risk factors for PCP were age less than a year (OR 6.34, 95%CI 1.86-21.65), HIV infection (OR 2.99, 95%CI 1.16-7.70), grunting (OR 2.64, 95%CI 1.04-6.73), and digital clubbing (OR 10.75, 95%CI 1.21-95.56). PCP is a common and life-threatening cause of severe pneumonia in Mozambican children. Mother-to-child HIV transmission prevention should be strengthened. Better diagnostic tools are needed