Fifteen-minute consultation: An approach to the management of PIMS-TS in a district general hospital.

The COVID-19 pandemic has caused significant disease across the globe but children seem to be much less affected than adults. Coincidentally with the first wave of the pandemic, a cluster of children with fever, hyperinflammation and shock were identified, and this was first described as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) by the Royal College of Paediatrics and Child Health. Patients with this novel condition were transferred to tertiary centres for management, increasing the pressure in these hospitals that were already extremely busy. There are multiple challenges related to the identification of patients presenting with PIMS-TS given that they mimic multiple other well-known paediatric conditions, like Kawasaki disease and toxic shock syndrome. Investigations and admission criteria to a district general hospital (DGH) need to be well established, and clear guidance should be available for easy decision making in a busy paediatric emergency department. Furthermore, these children can deteriorate suddenly and rapidly; close monitoring is vital, and any deterioration must be taken seriously and addressed immediately. All children who present severely ill, with shock and multiorgan failure, should be retrieved to a paediatric intensive care unit. As our knowledge of the condition has developed, more patients are now managed in a DGH, with virtual multidisciplinary team involvement. This paper outlines a structured approach to management of children presenting with suspected PIMS-TS in a DGH.

The Malawi Developmental Assessment Tool (MDAT): the creation, validation, and reliability of a tool to assess child development in rural African settings.

BACKGROUND: Although 80% of children with disabilities live in developing countries, there are few culturally appropriate developmental assessment tools available for these settings. Often tools from the West provide misleading findings in different cultural settings, where some items are unfamiliar and reference values are different from those of Western populations. METHODS AND FINDINGS: Following preliminary and qualitative studies, we produced a draft developmental assessment tool with 162 items in four domains of development. After face and content validity testing and piloting, we expanded the draft tool to 185 items. We then assessed 1,426 normal rural children aged 0-6 y from rural Malawi and derived age-standardized norms for all items. We examined performance of items using logistic regression and reliability using kappa statistics. We then considered all items at a consensus meeting and removed those performing badly and those that were unnecessary or difficult to administer, leaving 136 items in the final Malawi Developmental Assessment Tool (MDAT). We validated the tool by comparing age-matched normal children with those with malnutrition (120) and neurodisabilities (80). Reliability was good for items remaining with 94%-100% of items scoring kappas >0.4 for interobserver immediate, delayed, and intra-observer testing. We demonstrated significant differences in overall mean scores (and individual domain scores) for children with neurodisabilities (35 versus 99 [p<0.001]) when compared to normal children. Using a pass/fail technique similar to the Denver II, 3% of children with neurodisabilities passed in comparison to 82% of normal children, demonstrating good sensitivity (97%) and specificity (82%). Overall mean scores of children with malnutrition (weight for height <80%) were also significantly different from scores of normal controls (62.5 versus 77.4 [p<0.001]); scores in the separate domains, excluding social development, also differed between malnourished children and controls. In terms of pass/fail, 28% of malnourished children versus 94% of controls passed the test overall. CONCLUSIONS: A culturally relevant developmental assessment tool, the MDAT, has been created for use in African settings and shows good reliability, validity, and sensitivity for identification of children with neurodisabilities.

Comparison of previous and present World Health Organization clinical staging criteria in HIV-infected Malawian children.

In many settings, HIV infected children are looked after with limited access to CD4 cell count or viral load. The decision to initiate antiretroviral therapy (ART) is made clinically, based on the WHO paediatric staging criteria, which were revised in 2006. Results of using new and old criteria were compared. Of 694 children, 626 (90.2%) fulfilled criteria to start ART when applying the new WHO staging guidelines, whereas 330 (47.6%) children were eligible for ART when using the old WHO criteria. This signifies a marked rise in the number of paediatric patients qualifying for ART on clinical grounds.

Open-label comparative clinical study of chlorproguanil-dapsone fixed dose combination (Lapdap) alone or with three different doses of artesunate for uncomplicated Plasmodium falciparum malaria.

UNLABELLED: The objective of this study was to determine the appropriate dose of artesunate for use in a fixed dose combination therapy with chlorproguanil-dapsone (CPG-DDS) for the treatment of uncomplicated falciparum malaria. METHODS: Open-label clinical trial comparing CPG-DDS alone or with artesunate 4, 2, or 1 mg/kg at medical centers in Blantyre, Malawi and Farafenni, The Gambia. The trial was conducted between June 2002 and February 2005, including 116 adults (median age 27 years) and 107 children (median age 38 months) with acute uncomplicated Plasmodium falciparum malaria. Subjects were randomized into 4 groups to receive CPG-DDS alone or plus 4, 2 or 1 mg/kg of artesunate once daily for 3 days. Assessments took place on Days 0-3 in hospital and follow-up on Days 7 and 14 as out-patients. Efficacy was evaluated in the Day 3 per-protocol (PP) population using mean time to reduce baseline parasitemia by 90% (PC90). A number of secondary outcomes were also included. Appropriate artesunate dose was determined using a pre-defined decision matrix based on primary and secondary outcomes. Treatment emergent adverse events were recorded from clinical assessments and blood parameters. Safety was evaluated in the intent to treat (ITT) population. RESULTS: In the Day 3 PP population for the adult group (N = 85), mean time to PC90 was 19.1 h in the CPG-DDS group, significantly longer than for the +artesunate 1 mg/kg (12.5 h; treatment difference -6.6 h [95%CI -11.8, -1.5]), 2 mg/kg (10.7 h; -8.4 h [95%CI -13.6, -3.2]) and 4 mg/kg (10.3 h; -8.7 h [95%CI -14.1, -3.2]) groups. For children in the Day 3 PP population (N = 92), mean time to PC90 was 21.1 h in the CPG-DDS group, similar to the +artesunate 1 mg/kg group (17.7 h; -3.3 h [95%CI -8.6, 2.0]), though the +artesunate 2 mg/kg and 4 mg/kg groups had significantly shorter mean times to PC90 versus CPG-DDS; 14.4 h (treatment difference -6.4 h [95%CI -11.7, -1.0]) and 12.8 h (-7.4 h [95%CI -12.9, -1.8]), respectively. An analysis of mean time to PC90 for the Day 14 PP and ITT populations was consistent with the primary analysis. Treatment emergent, drug-related adverse events were experienced in 35.3% (41/116) of adults and 70.1% (75/107) of children; mostly hematological and gastroenterological. The nature and incidence of adverse events was similar between the groups. No dose-related changes in laboratory parameters were observed. Nine serious adverse events due to any cause occurred in five subjects including two cases of hemolysis believed to be associated with drug treatment (one adult, one child). One adult died of anaphylactic shock, not associated with investigational therapy. CONCLUSIONS: CPG-DDS plus artesunate demonstrated advantages over CPG-DDS alone for the primary efficacy endpoint (mean time to PC90) except in children for the 1 mg/kg artesunate dose. Based on a pre-defined decision matrix, the primary endpoint in the child group supported an artesunate dose of 4 mg/kg. Secondary endpoints also supported a 4 mg/kg artesunate dose to take forward into the remainder of the development program. TRIAL REGISTRATION: ClinicalTrials.gov NCT00519467.