International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis.

OBJECTIVE: To create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE). METHODS: After selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ≥75% agreement). RESULTS: Corticosteroids are recommended in all children with NMDARE (pulsed IV preferred), with additional IV immunoglobulin or plasma exchange in severe patients. Prolonged first-line immunotherapy can be offered for up to 3-12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about 2 weeks after first-line initiation. Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. Maintenance immune suppression beyond 6 months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), which is dictated by the severity and clinical course (i.e., median 3, 9 and 18 months in the best, average, and worst responders, respectively). Recommendations on the timing of oncologic searches are provided. CONCLUSION: These international consensus recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients

Addressing the challenges and relational aspects of index-linked HIV testing for children and adolescents: insights from the B-GAP study in Zimbabwe.

INTRODUCTION: Index-linked HIV testing, targeted at sexual contacts or children of individuals with HIV, may improve yield and efficiency. The B-GAP study evaluated index-linked testing approaches in health facility and community-based settings. This paper reports on a qualitative study to understand factors that affect uptake of index-linked HIV testing for children and adolescents. METHODS: We conducted four focus group discussions (FGDs) with caregivers who had their children tested through B-GAP and one FGD with providers who offered index-linked HIV testing to indexes. We aimed to understand enabling and inhibiting factors in the decision-making process. Translated and transcribed transcripts were read for familiarisation. Following initial coding, analytical memos were written to identify emerging key themes across the data. RESULTS: Our findings showed there was inadequate emphasis on paediatric HIV in routine care which had a negative impact on subsequent uptake of testing for children. Once the decision to test had been made, access to facilities was sometimes challenging and alleviated by community-based testing. A key finding was that HIV testing is not a discrete event but a process that was influenced by relationships with other family members and children themselves. These relationships raised complex issues that could prevent or delay the testing process. CONCLUSION: There is a need to improve messaging on the importance of HIV testing for children and adolescents and to provide support to caregivers and their families in order to improve testing uptake. Addressing access barriers through the provision of community-based testing and implementing a family-centred approach can optimise index-linked testing

A comparison of parenteral phenobarbital vs. parenteral phenytoin as second-line management for pediatric convulsive status epilepticus in a resource-limited setting

Introduction: Pediatric convulsive status epilepticus (CSE) which is refractory to first-line benzodiazepines is a significant clinical challenge, especially within resource-limited countries. Parenteral phenobarbital is widely used in Africa as second-line agent for pediatric CSE, however evidence to support its use is limited. Purpose: This study aimed to compare the use of parenteral phenobarbital against parenteral phenytoin as a second-line agent in the management of pediatric CSE. Methodology: An open-labeled single-center randomized parallel clinical trial was undertaken which included all children (between ages of 1 month and 15 years) who presented with CSE. Children were allocated to receive either parenteral phenobarbital or parenteral phenytoin if they did not respond to first-line benzodiazepines. An intention-to-treat analysis was performed with the investigators blinded to the treatment arms. The primary outcome measure was the success of terminating CSE. Secondary outcomes included the need for admission to the pediatric intensive care unit (PICU) and breakthrough seizures during the admission. In addition, local epidemiological data was collected on the burden of pediatric CSE. Results: Between 2015 and 2018, 193 episodes of CSE from 111 children were enrolled in the study of which 144 met the study requirements. Forty-two percent had a prior history of epilepsy mostly from structural brain pathology (53%). The most common presentation was generalized CSE (65%) caused by acute injuries or infections of the central nervous system (59%), with 19% of children having febrile status epilepticus. Thirty-five percent of children required second-line management. More patients who received parenteral phenobarbital were at a significantly reduced risk of failing second-line treatment compared to those who received parenteral phenytoin (RR = 0.3, p = 0.0003). Phenobarbital also terminated refractory CSE faster (p &lt; 0.0001). Furthermore, patients who received parenteral phenobarbital were less likely to need admission to the PICU. There was no difference between the two groups in the number of breakthrough seizures that occurred during admission. Conclusion: Overall this study supports anecdotal evidence that phenobarbital is a safe and effective second-line treatment for the management of pediatric CSE. These results advocate for parenteral phenobarbital to remain available to health care providers managing pediatric CSE in resource-limited settings. Attachments: CONSORT 2010 checklist Trial registration: NCT03650270 Full trial protocol available: https://clinicaltrials.gov/ct2/show/NCT03650270?recrs=e&amp;type;=Intr&amp;cond=Status+Epilepticus&amp;age;=0&amp;rank=1</p

A comparison of parenteral phenobarbital vs. parenteral phenytoin as second-line management for pediatric convulsive status epilepticus in a resource-limited setting

Introduction:andnbsp;Pediatric convulsive status epilepticus (CSE) which is refractory to first-line benzodiazepines is a significant clinical challenge, especially within resource-limited countries. Parenteral phenobarbital is widely used in Africa as second-line agent for pediatric CSE, however evidence to support its use is limited. Purpose:andnbsp;This study aimed to compare the use of parenteral phenobarbital against parenteral phenytoin as a second-line agent in the management of pediatric CSE. Methodology:andnbsp;An open-labeled single-center randomized parallel clinical trial was undertaken which included all children (between ages of 1 month and 15 years) who presented with CSE. Children were allocated to receive either parenteral phenobarbital or parenteral phenytoin if they did not respond to first-line benzodiazepines. An intention-to-treat analysis was performed with the investigators blinded to the treatment arms. The primary outcome measure was the success of terminating CSE. Secondary outcomes included the need for admission to the pediatric intensive care unit (PICU) and breakthrough seizures during the admission. In addition, local epidemiological data was collected on the burden of pediatric CSE. Results:andnbsp;Between 2015 and 2018, 193 episodes of CSE from 111 children were enrolled in the study of which 144 met the study requirements. Forty-two percent had a prior history of epilepsy mostly from structural brain pathology (53%). The most common presentation was generalized CSE (65%) caused by acute injuries or infections of the central nervous system (59%), with 19% of children having febrile status epilepticus. Thirty-five percent of children required second-line management. More patients who received parenteral phenobarbital were at a significantly reduced risk of failing second-line treatment compared to those who received parenteral phenytoin (RRandnbsp;= 0.3,andnbsp;pandnbsp;= 0.0003). Phenobarbital also terminated refractory CSE faster (pandnbsp;andlt; 0.0001). Furthermore, patients who received parenteral phenobarbital were less likely to need admission to the PICU. There was no difference between the two groups in the number of breakthrough seizures that occurred during admission. Conclusion:andnbsp;Overall this study supports anecdotal evidence that phenobarbital is a safe and effective second-line treatment for the management of pediatric CSE. These results advocate for parenteral phenobarbital to remain available to health care providers managing pediatric CSE in resource-limited settings. Attachments:andnbsp;CONSORT 2010 checklist Trial registration:andnbsp;NCT03650270 Full trial protocol available:andnbsp;https://clinicaltrials.gov/ct2/show/NCT03650270?recrs=eandamp;type=Intrandamp;cond=Status+Epilepticusandamp;age=0andamp;rank=1</p

Assessing salinization of coastal groundwater by tidal action: The tropical Wouri Estuary, Douala, Cameroon

Study region: Douala, Cameroon, West Africa. Study focus: Salinity of shallow coastal groundwater in Douala, Cameroon impairs its use for drinking and industrial purposes. Previous studies suggest that salinization is from tidal flooding from the Wouri Estuary. We aimed to test the tidal origin of groundwater salinization by conducting a time series investigation of water level and salinity, and assessed the stable water isotopes (δ¹⁸O and δD) and major cations (Ca²+ and Mg²+) in groundwater and adjacent estuarine tidal creek. During the time series measurements, we pumped groundwater for over 5 tidal cycles to induce flow into a test well. New hydrologic insights for the region: The time-series groundwater level mimicked water level changes in the estuary. However, the temporal salinity in groundwater did not correspond to tidal salinity changes of estuarine water, indicating that estuarine water did not intrude groundwater. The δ¹⁸O and δD of the groundwater and estuarine samples are collinear and fall along the local meteoric water line of Douala and had d-excesses of >10, indicating a non-evaporated rain recharge of groundwater or lack of salinization by evapoconcentration. The salinity-δ¹⁸O relationship showed that the origin of salinity in the coastal groundwater aquifer is not from seawater intrusion. The Mg²+/Ca²+ ratios of <1 in groundwater compared to 6–8 in estuarine water support the non-seawater origin of groundwater salinity. We conclude that the salinity of coastal groundwater in Douala is not affected by tide-induced salinization from the adjacent Wouri Estuary but by geogenic sources in the aquifer

Tide-salinity patterns reveal seawater-freshwater mixing behavior at a river mouth and tidal creeks in a tropical mangrove estuary

Tide and salinity data collected at minute intervals over multiple semidiurnal tides were used to investigate the source of water (e.g., seawater, river, groundwater and rain) and their relative timing in mixing at the mouth of a river, a tidal creek at mid-estuary and a tidal creek at the shoreline at the head of a tropical mangrove estuary. Our objectives were to document the temporal changes in tide induced water level changes and salinity at each location and to use the relationship between salinity and water level to elucidate the sources of water and the timing of different sources of water in the hydrologic mixing processes. The data trends in tide vs. salinity (T-S) plots for the river mouth revealed mixing with seawater during rising tides and freshwater diluted seawater (brackish) drainage from the mangrove forest during ebb tides. In the mangrove creek at mid-estuary, the data trends in the T-S plots for rising tides initially showed constant salinity, followed by sharp rises in salinity to peak tide caused by seawater intrusion. The salinity decreased precipitously at the start of tidal ebbing due to influx of freshwater (rain) diluted brackish water from the mangrove forest. The data trends in the T-S plots for the tidal creek at the shoreline located at the estuary head showed constant salinity which decreased only near peak rising tide because of river dilution. During tidal ebbing, the salinity further decreased from groundwater influx before increasing to background salinity, which stayed constant to low tide. Establishing T-S patterns for multiple locations in mangrove estuaries over sub-tidal to tidal scales define the expected salinity variations in seawater-freshwater mixing which can be used to (1) establish baseline hydrologic and salinity (hydrochemical) conditions for temporal and spatial assessments and (2) serve to guide short to long-term sampling regimes for scientific studies and estuarine ecosystem management

Analysis of a model of gambiense sleeping sickness in humans and cattle

Human African Trypanosomiasis (HAT) and Nagana in cattle, commonly called sleeping sickness, is caused by trypanosome protozoa transmitted by bites of infected tsetse flies. We present a deterministic model for the transmission of HAT caused by Trypanosoma brucei gambiense between human hosts, cattle hosts and tsetse flies. The model takes into account the growth of the tsetse fly, from its larval stage to the adult stage. Disease in the tsetse fly population is modeled by three compartments, and both the human and cattle populations are modeled by four compartments incorporating the two stages of HAT. We provide a rigorous derivation of the basic reproduction number $\mathcal{R}_{0}$ . For $\mathcal{R}_{0}1$ , HAT persists. Elasticity indices for $\mathcal{R}_{0}$ with respect to different parameters are calculated with baseline parameter values appropriate for HAT in West Africa; indicating parameters that are important for control strategies to bring $\mathcal{R}_{0}$ below 1. Numerical simulations with $\mathcal{R}_0 > 1$ show values for the infected populations at the endemic equilibrium, and indicate that with certain parameter values, HAT could not persist in the human population in the absence of cattle