Background A procoagulant state is implicated in cerebral malaria (CM) pathogenesis, but whether disseminated intravascular coagulation (DIC) is present or associated with fatal outcome is unclear. Objectives To determine the frequency of overt DIC according to International Society on Thrombosis and Haemostasis (ISTH) criteria, in children with fatal and non-fatal CM. Patients/Methods Malawian children were recruited into a prospective cohort study in the following diagnostic groups: retinopathy positive CM (n=140), retinopathy negative CM (n=36), non-malarial coma (n=14), uncomplicated malaria (n=91), mild non-malarial febrile illness (n=85) and healthy controls (n=36). Assays in the ISTH DIC criteria were measured together with 3 fibrin-related markers, protein C, antithrombin and soluble thrombomodulin. Results and Conclusions Data enabling assignment of the presence or absence of ‘overt DIC’ were available in 98/140 children with retinopathy positive CM. Overt DIC was present in 19 (19%) and was associated with fatal outcome (Odds ratio [OR] 3.068; 95% Confidence Interval [CI] 1.085-8.609; P=0.035). The three fibrin-markers and soluble thrombomodulin levels were higher in CM cases than uncomplicated malaria cases (all P=<0.001). Mean fibrin degradation product level was higher in fatal CM (71.3 [95% CI 49.0-93.6]) than non-fatal CM (48.0 [37.7-58.2]; P=0.032), but on multivariate logistic regression, thrombomodulin was the only coagulation related marker independently associated with fatal outcome (OR 1.084 [1.017 - 1.156]; P=0.014). Despite these laboratory derangements no child in the study had clinically evident bleeding or thrombosis. Overt DIC score and high thrombomodulin levels are associated with fatal outcome in CM, but infrequently indicate a consumptive coagulopathy.
Purpose Wilms tumor is a common renal cancer of childhood with long-term survival rates exceeding 80% in high-resource countries, yet survival remains below 50% in the low-resource settings of Africa. We assessed outcomes of a resource-adapted treatment protocol at a Malawian hospital to identify actionable factors affecting survival. Methods: We assessed clinical outcomes with a single-center retrospective cohort study of children diagnosed between 2016 and 2021 in Lilongwe, Malawi. Findings: We identified 136 patients with Wilms tumor, most commonly with stage III (25.7%) or IV disease (25.7%). Two-year overall survival (OS) was: Stage I, 78%; Stage II, 27%; Stage III, 62%; Stage IV, 23%, Stage V, 0%. Event-free survival (EFS) was: Stage I, 60%; Stage II, 0%; Stage III, 51%; Stage IV, 13%; Stage V, 0%. After death, treatment abandonment was the most common event comprising EFS, occurring in 26.5% of patients. Among 43% of patients who completed therapy, 2-year OS was 80% and EFS was 69%. Relapse was documented in 9.6% of patients. Radiotherapy was indicated for 40.4% patients, among whom only three received it due to regional unavailability. Factors associated with OS were severe acute malnutrition (Hazard ratio, HR, 1.9), increasing tumor stage (HR, 1.5), and inferior vena cava involvement (HR, 2.7). On multivariable analysis, only tumor stage remained associated with outcome. Interpretation Implementing a curative resource-adapted treatment protocol in an extremely resourced-constrained environment was feasible in Malawi and resulted in relatively favorable outcomes in low-stage disease, particularly among those who completed therapy. However, factors such as late-stage disease, frequent abandonment, and absent radiotherapy represent ongoing implementation barriers that should be the focus of continued research funding and intervention in Africa.
Introduction: Wilms tumor therapy in low-and middle-income countries (LMICs) relies on treatment protocols adapted to resource limitations, but these protocols have rarely been evaluated in real-world settings. Such evaluations are necessary to identify high-impact research priorities for clinical and implementation trials in LMICs. The purpose of this study was to identify highest priority targets for future clinical and implementation trials in sub-Saharan Africa by assessing outcomes of a resource-adapted treatment protocol in Malawi. Methods: We conducted a retrospective cohort study of children treated for Wilms tumor with an adapted SIOP-backbone protocol in Lilongwe, Malawi between 2016 and 2021. Survival analysis assessed variables associated with poor outcome with high potential for future research and intervention. Results: We identified 136 patients, most commonly with stage III (n = 35; 25.7%) orIV disease (n = 35; 25.7%). Two-year event-free survival (EFS) was 54% for stage I/II, 51% for stage III, and 13% for stage IV. A single patient with stage V disease survived to 1 year. Treatment abandonment occurred in 36 (26.5%) patients. Radiotherapy was indicated for 55 (40.4%), among whom three received it. Of these 55 patients, 2-year EFS was 31%. Of 14 patients with persistent metastatic pulmonary disease at the time of nephrectomy, none survived to 2 years. Notable variables independently associated with survival were severe acute malnutrition (hazard ratio [HR]: 1.9), increasing tumor stage (HR: 1.5), and vena cava involvement (HR: 3.1). Conclusion:High-impact targets for clinical and implementation trials in low-resource settings include treatment abandonment, late presentation, and approaches optimized for healthcare systems with persistently unavailable radiotherapy.
Objectives The Kaposi sarcoma (KS) T0 versus T1 staging classification does not address the unique clinical features of paediatric KS in human gammaherpesvirus 8 (HHV‐8) endemic regions of Africa. This study seeks to define patterns of childhood KS using a paediatric‐specific approach. Methods The Lilongwe paediatric KS staging classification categorizes disease based on clinical phenotype: stage 1 = mild/moderate KS limited to cutaneous/oral involvement, stage 2 = primarily lymphadenopathic disease, stage 3 = woody edema KS, stage 4 = visceral and/or severe/disseminated mucocutaneous disease. Characteristics and outcomes were evaluated from paediatric referral centres in Lilongwe, Malawi, and Mbeya, Tanzania. Results Among 171 patients, the median age was 9.3 years, 37% (n = 63) were female, and 87% (n = 149) had HIV. Breakdown by stage was as follows: 18% (n = 31) stage 1, 33% (n = 56) stage 2, 19% (n = 33) stage 3, and 30% (n = 51) stage 4. Age (younger stage 2 and older stage 3), severe CD4 count suppression (lower CD4 for stages 1 and 4), and presence of severe anaemia and thrombocytopenia (worse for stages 2 and 4) differed across stages. Estimated 2‐year event‐free survival/progression‐free survival/overall survival by stage was as follows: stage 1, 81%/81%/87%; stage 2, 50%/50%/63%; stage 3, 24%/49%/81%; and stage 4, 29%/34%/54%. Sub‐analysis of stage 2 lymphadenopathic KS demonstrated superior long‐term 6‐year event‐free survival of 70% (95% confidence interval [CI] 49–83) for younger children (aged <7 years) versus 27% (95% CI 8–51) for older children. Conclusions This paediatric‐specific staging classification categorizes patients with distinct characteristics and patterns of treatment response. This platform may guide clinicians to provide risk‐stratified treatment with the hope of improving survival among children with KS.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.