Treatment Access for Gastrointestinal Stromal Tumor in Predominantly Low- and Middle-Income Countries.

Importance: Gastrointestinal stromal tumor (GIST) is a rare cancer treated with the tyrosine kinase inhibitors imatinib mesylate or sunitinib malate. In general, in low- and middle-income countries (LMICs), access to these treatments is limited. Objective: To describe the demographic characteristics, treatment duration, and survival of patients with GIST in LMICs treated with imatinib and sunitinib through The Max Foundation programs. Design, Setting, and Participants: This retrospective database cohort analysis included patients in 2 access programs administered by The Max Foundation: the Glivec International Patient Assistance Program (GIPAP), from January 1, 2001, to December 31, 2016, and the Max Access Solutions (MAS) program, January 1, 2017, to October 12, 2020. Sixty-six countries in which The Max Foundation facilitates access to imatinib and sunitinib were included. Participants consisted of patients with approved indications for imatinib, including adjuvant therapy in high-risk GIST by pathologic evaluation of resected tumor or biopsy-proven unresectable or metastatic GIST. All patients were reported to have tumors positive for CD117(c-kit) by treating physicians. A total of 9866 patients received treatment for metastatic and/or unresectable disease; 2100 received adjuvant imatinib; 49 received imatinib from another source and were only included in the sunitinib analysis; and 53 received both imatinib and sunitinib through The Max Foundation programs. Data were analyzed from October 13, 2020, to January 30, 2024. Main Outcomes and Measures: Demographic and clinical information was reported by treating physicians. Kaplan-Meier analysis was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). An imputation-based informed censoring model estimated events for patients lost to follow-up after treatment with adjuvant imatinib. Patients who were lost to follow-up with metastatic or unresectable disease were presumed deceased. Results: A total of 12 015 unique patients were included in the analysis (6890 male [57.6%]; median age, 54 [range, 0-100] years). Of these, 2100 patients were treated with imatinib in the adjuvant setting (median age, 54 [range 8-88] years) and 9866 were treated with imatinib for metastatic or unresectable disease (median age, 55 [range, 0-100] years). Male patients comprised 5867 of 9866 patients (59.5%) with metastatic or unresectable disease and 1023 of 2100 patients (48.7%) receiving adjuvant therapy. The median OS with imatinib for unresectable or metastatic disease was 5.8 (95% CI, 5.6-6.1) years, and the median TTD was 4.2 (95% CI, 4.1-4.4) years. The median OS with sunitinib for patients with metastatic or unresectable GIST was 2.0 (95% CI, 1.5-2.5) years; the median TTD was 1.5 (95% CI, 1.0-2.1) years. The 10-year OS rate in the adjuvant setting was 73.8% (95% CI, 67.2%-81.1%). Conclusions and Relevance: In this cohort study of patients with GIST who were predominantly from LMICs and received orally administered therapy through the GIPAP or MAS programs, outcomes were similar to those observed in high-resource countries. These findings underscore the feasibility and relevance of administering oral anticancer therapy to a molecularly defined population in LMICs, addressing a critical gap in cancer care.

The impact of cytokine levels in young South African children with and without HIV-associated acute lower respiratory infections.

Altered host immune responses are considered to play a key role in the pathogenesis of acute lower respiratory infections (ALRI). The existing literature on cytokine responses in ALRI is largely focussed on adults from developed countries and there are few reports describing the role of cytokines in childhood ALRI, particularly in African or human immunodeficiency virus (HIV)-infected populations. To measure systemic cytokine levels in blood plasma from young South African children with and without ALRI and with and without HIV to determine associations between cytokine responses and disease status and respiratory viral identification. Blood plasma samples were collected from 106 hospitalized ALRI cases and 54 non-ALRI controls less than 2 years of age. HIV status was determined. Blood plasma concentrations of 19 cytokines, 7 chemokines, and 4 growth factors (epidermal growth factor, fibroblast growth factor-basic, hepatocyte growth factor, and vascular endothelial) were measured using The Human Cytokine 30-Plex Panel. Common respiratory viruses were identified by PCR. Mean cytokine concentrations for G-CSF, interferon (IFN)-γ, interleukin (IL)-5, and MCP-1 were significantly higher in ALRI cases than in nonrespiratory controls. Within the ALRI cases, several cytokines were higher in children with a virus compared with children without a virus. Mean cytokine concentrations for IFN-α, IFN-γ, IL-4, IL-5, IL-13, tumour necrosis factor-α, and MIP-1α were significantly lower in HIV-infected cases than in HIV-uninfected cases, while IP-10 and monokine induced by interferon-γ were significantly higher in HIV-infected cases than in HIV-uninfected cases. Certain cytokines are likely to play an important role in the host immune response to ALRI. HIV-infected children have impaired inflammatory responses to respiratory infections compared with HIV-uninfected children.

Testing the socioeconomic and environmental determinants of better child-health outcomes in Africa: a cross-sectional study among nations.

OBJECTIVE: We sought to test hypotheses regarding the principal correlates of child-health performance among African nations based on previous evidence collected at finer spatial scales. DESIGN: Retrospective, cross-sectional study. SETTING: All countries in Africa, excluding small-island nations. PRIMARY AND SECONDARY OUTCOME MEASURES: We defined a composite child-health indicator for each country comprising the incidence of stunting, deaths from respiratory disease, deaths from diarrhoeal disease, deaths from other infectious disease and deaths from injuries for children aged under 5 years. We also compiled national-level data for Africa to test the effects of country-level water quality, air pollution, food supply, breast feeding, environmental performance, per capita wealth, healthcare investment, population density and governance quality on the child-health indicator. RESULTS: Across nations, child health was lowest when water quality, improved sanitation, air quality and environmental performance were lowest. There was also an important decline in child health as household size (a proxy for population density) increased. The remaining variables had only weak effects, but in the directions we hypothesised. CONCLUSIONS: These results emphasise the importance of continued investment in clean water and sanitation services, measures to improve air quality and efforts to restrict further environmental degradation, to promote the UN's Sustainable Development Goal 3 target to '… end preventable deaths of newborns and children under 5' and Goal 6 to '… ensure access to water and sanitation for all' by 2030.

Rhinovirus C is associated with wheezing and rhinovirus A is associated with pneumonia in hospitalized children in Morocco.

Human rhinovirus (RV) is commonly associated with severe acute lower respiratory infections (ALRI) in children. We aimed to describe the distribution of RV species and associations between RV species and clinical features in children hospitalized with clinically severe pneumonia (CSP) in Morocco. Nasopharyngeal aspirates (NPAs) were collected from 700 children, 2-59 months of age, admitted with CSP to the Hôpital d'Enfants de Rabat in Morocco. At least one respiratory virus was identified in 92% of children, of which RV was the most common (53%). PCR assays, sequencing, and phylogenetic tree analyses were carried out on 183 RV-positive NPAs to determine RV species and genotypes. Of 157 successfully genotyped NPAs, 60 (38.2%) were RV-A, 8 (5.1%) were RV-B, and 89 (56.7%) were RV-C. Wheezing and cyanosis were more common in RV-C-positive than RV-A-positive children (80.9% vs. 56.7%; P = 0.001 for wheezing and 10.1% vs. 0%; P = 0.011 for cyanosis). Physician's discharge diagnosis of pneumonia was more frequent among RV-A-positive (40.0%) than RV-C-positive children (20.2%; P = 0.009). RV-A and RV-C showed distinct seasonal patterns. Our findings suggest that RV-C is associated with wheezing illness while RV-A is associated with pneumonia. J. Med. Virol. 89:582-588, 2017. © 2016 Wiley Periodicals, Inc.

Rhinovirus species and clinical features in children hospitalised with pneumonia from Mozambique.

OBJECTIVES: To describe the prevalence of human rhinovirus (RV) species in children hospitalised with pneumonia in Manhiça, Mozambique, and the associations between RV species and demographic, clinical and laboratory features. METHODS: Nasopharyngeal aspirates were collected from children 0 to 10 years of age (n = 277) presenting to Manhiça District Hospital with clinical pneumonia. Blood samples were collected for HIV and malaria testing, blood culture and full blood counts, and a chest X-ray was performed. A panel of common respiratory viruses was investigated using two independent multiplex RT-PCR assays with primers specific for each virus and viral type. RV species and genotypes were identified by seminested PCR assays, sequencing and phylogenetic tree analyses. RESULTS: At least one respiratory virus was identified in 206 (74.4%) children hospitalised with clinical pneumonia. RV was the most common virus identified in both HIV-infected (17 of 38, 44.7%) and HIV-uninfected (74 of 237, 31.2%; P = 0.100) children. RV-A was the most common RV species identified (47 of 275, 17.0%), followed by RV-C (35/275, 12.6%) and RV-B (8/275, 2.9%). Clinical presentation of the different RV species was similar and overlapping, with no particular species being associated with specific clinical features. CONCLUSIONS: RV-A and RV-C were the most common respiratory viruses identified in children hospitalised with clinical pneumonia in Manhiça. Clinical presentation of RV-A and RV-C was similar and overlapping.

Respiratory viruses in young South African children with acute lower respiratory infections and interactions with HIV.

BACKGROUND: Human rhinovirus (RV) is the most common respiratory virus and has been associated with frequent and severe acute lower respiratory infections (ALRI). The prevalence of RV species among HIV-infected children in South Africa is unknown. OBJECTIVES: To describe the prevalence of respiratory viruses, including RV species, associated with HIV status and other clinical symptoms in children less than two years of age with and without ALRI in Pretoria, South Africa. STUDY DESIGN: Nasopharyngeal aspirates were collected from 105 hospitalized ALRI cases and 53 non-ALRI controls less than two years of age. HIV status was determined. Common respiratory viruses were identified by PCR, and RV species and genotypes were identified by semi-nested PCR, sequencing and phylogenetic tree analyses. RESULTS: Respiratory viruses were more common among ALRI cases than controls (83.8% vs. 69.2%; p=0.041). RV was the most commonly identified virus in cases with pneumonia (45.6%) or bronchiolitis (52.1%), regardless of HIV status, as well as in controls (39.6%). RV-A was identified in 26.7% of cases and 15.1% of controls while RV-C was identified in 21.0% of cases and 18.9% of controls. HIV-infected children were more likely to be diagnosed with pneumonia than bronchiolitis (p<0.01). RSV was not identified in any HIV-infected cases (n=15) compared with 30.6% of HIV-uninfected cases (n=85, p=0.013), and was identified more frequently in bronchiolitis than in pneumonia cases (43.8% vs. 12.3%; p<0.01). CONCLUSIONS: RV-A and RV-C are endemic in South African children and HIV infection may be protective against RSV and bronchiolitis.

Epidemiology, etiology, x-ray features, importance of co-infections and clinical features of viral pneumonia in developing countries.

Pneumonia is still the number one killer of young children globally, accounting for 18% of mortality in children under 5 years of age. An estimated 120 million new cases of pneumonia occur globally each year. In developing countries, management and prevention efforts against pneumonia have traditionally focused on bacterial pathogens. More recently however, viral pathogens have gained attention as a result of improved diagnostic methods, such as polymerase chain reaction, outbreaks of severe disease caused by emerging pathogens, discovery of new respiratory viruses as well as the decrease in bacterial pneumonia as a consequence of the introduction of highly effective conjugate vaccines. Although the epidemiology, etiology and clinical characterization of viral infections are being studied extensively in the developed world, little data are available from low- and middle-income countries. In this paper, we review the epidemiology, etiology, clinical and radiological features of viral pneumonia in developing countries.

Prevalence of and risk factors for human rhinovirus infection in healthy aboriginal and non-aboriginal Western Australian children.

BACKGROUND: Human rhinovirus (HRV) species C (HRV-C) have been associated with frequent and severe acute lower respiratory infections and asthma in hospitalized children. The prevalence of HRV-C among healthy children and whether this varies with ethnicity is unknown. OBJECTIVE: To describe the prevalence of HRV species and their associations with demographic, environmental and socioeconomic factors in healthy Aboriginal and non-Aboriginal children. METHODS: Respiratory viruses and bacteria were identified in 1006 nasopharyngeal aspirates collected from a cohort of 79 Aboriginal and 88 non-Aboriginal Western Australian children before 2 years of age. HRV-positive nasopharyngeal aspirates were typed for HRV species and genotypes. Longitudinal growth models incorporating generalized estimating equations were used to investigate associations between HRV species and potential risk factors. RESULTS: Of the 159 typed specimens, we identified 83 (52.2%) human rhinovirus species A (HRV-A), 26 (16.4%), human rhinovirus species B and 50 (31.4%) HRV-C. HRV-C was associated with upper respiratory symptoms in Aboriginal (odds ratio, 3.77; 95% confidence interval:1.05-13.55) and non-Aboriginal children (odds ratio, 5.85; 95% confidence interval: 2.33-14.66). HRV-A and HRV-C were associated with carriage of respiratory bacteria. In Aboriginal children, HRV-A was more common in the summer and in those whose mothers were employed prior to delivery. In non-Aboriginal children, day-care attendance and exclusive breast-feeding at age 6-8 weeks were associated with detection of HRV-A, and gestational smoking with detection of HRV-C. CONCLUSIONS: Factors associated with the presence of HRV differ between Aboriginal and non-Aboriginal children. In contrast to HRV-A, HRV-C is associated with upper respiratory symptoms suggesting that HRV-C is likely to be implicated in respiratory illness.