Treatment strategies for Kaposi sarcoma in sub-Saharan Africa

The global burden of sepsis is concentrated in sub-Saharan Africa, where extensive pathogen diversity and limited laboratory capacity challenge targeted antimicrobial management of life-threatening infections. In this context, established and emerging rapid pathogen diagnostics may stratify sepsis patients into subgroups with prognostic and therapeutic relevance. In a prospective cohort of adults (age ≥18 years) hospitalized with suspected sepsis in Uganda, we stratified patients using rapid diagnostics for HIV, tuberculosis (TB), malaria, and influenza, and compared clinical characteristics and 30-day outcomes across these pathogen-driven subgroups. From April 2017 to August 2019, 301 adults were enrolled (median age, 32 years [interquartile range, 26–42 years]; female, n = 178 [59%]). A total of 157 patients (53%) were HIV infected. Sixty-one patients (20%) tested positive for malaria, 52 (17%), for TB (including 49 of 157 [31%] HIV-infected patients), and 17 (6%), for influenza. Co-infection was identified in 33 (11%) patients. The frequency of multi-organ failure, including shock and acute respiratory failure, was greatest among patients with HIV-associated TB. Mortality at 30 days was 19% among patients with malaria, 40% among patients with HIV-associated TB, 32% among HIV-infected patients without microbiological evidence of TB, 6% among patients with influenza, and 11% among patients without a pathogen identified. Despite improvements in anti-retroviral delivery, the burden of sepsis in Uganda remains concentrated among young, HIV-infected adults, with a high incidence of severe HIV-associated TB. In parallel with improvements in acute-care capacity, use of rapid pathogen diagnostics may enhance triage and antimicrobial management during emergency care for sepsis in sub-Saharan Africa, and could be used to enrich study populations when trialing pathogen-specific treatment strategies in the region.

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PO 8719 INTRODUCING A NEW AFRICA MENINGITIS NETWORK – A NORTH-SOUTH COLLABORATION

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.165 ◽

2019 ◽

Vol 4 (Suppl 3) ◽

pp. A63.1-A63

Author(s):

Mosepele Mosepele ◽

Cecilia Kanyama ◽

David Meya ◽

Fiona Cresswell ◽

Timothee Chammard ◽

...

Keyword(s):

Treatment Strategies ◽

Sub Saharan Africa ◽

High Dose ◽

Diagnostic Strategies ◽

Cns Infections ◽

Study Protocols ◽

Sub Saharan ◽

Novel Treatment Strategies ◽

Set Up ◽

Randomised Controlled

BackgroundCentral nervous system infections, including meningitis, continue to cause significant morbidity in Africa. HIV has contributed to the epidemiology of CNS infections in this setting. Notable advances in the study of CNS infections by several groups have demonstrated the utility of new diagnostic strategies and impact of novel treatment strategies. However, efforts to coordinate meningitis research in Africa, and between Africa and the rest of the world remain very limited.MethodsIn a bid to promote a coordinated study of CNS infections across Africa, and in collaboration with other meningitis groups globally, the researchers of the AMBITION study (High Dose Ambisome on a Fluconazole Backbone for Cryptococcal Meningitis Induction Therapy in Sub-saharan Africa: A Randomised Controlled Non-inferiority Trial) are leveraging the EDCTP support for the AMBITION trial to set up an Africa Meningitis Trials Network.ResultsThe Africa Meningitis Trials Network (AMNET) was launched in Malawi in early 2018. Main achievements since the launch of the network, include an internal review of meningitis research across network sites and launch of the network website. The network also has two study protocols pending ethics review at all sites. These studies will provide much needed information on resources available for meningitis care, research and provide a baseline epidemiology of meningitis in Africa.ConclusionAMNET provides a rare opportunity for investigators interested in meningitis research to leverage the ongoing AMBITION trial to conduct Africa-wide preliminary research on meningitis. The network is recruiting additional members in Africa and globally to collaborate on meningitis research, and also apply for research funding to support meningitis work. Anyone interested in knowing more about the network should contact the AMNET communications officer, Ms Phum’lani Machao, [email protected]

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Transmission of Kaposi sarcoma-associated herpesvirus in sub-Saharan Africa

AIDS ◽

10.1097/qad.0b013e3282f4352e ◽

2008 ◽

Vol 22 (4) ◽

pp. 535-537 ◽

Cited By ~ 6

Author(s):

Sam M Mbulaiteye ◽

James J Goedert

Keyword(s):

Kaposi Sarcoma ◽

Sub Saharan Africa ◽

Sub Saharan

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Pediatric Kaposi sarcoma in context of the HIV epidemic in sub-Saharan Africa: current perspectives

Pediatric Health Medicine and Therapeutics ◽

10.2147/phmt.s142816 ◽

2018 ◽

Vol Volume 9 ◽

pp. 35-46 ◽

Cited By ~ 11

Author(s):

Nader Kim El-Mallawany ◽

Casey L McAtee ◽

Liane R Campbell ◽

Peter N Kazembe

Keyword(s):

Kaposi Sarcoma ◽

Sub Saharan Africa ◽

Hiv Epidemic ◽

Sub Saharan

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Viral and immunological markers of HIV-associated Kaposi sarcoma recurrence

PLoS ONE ◽

10.1371/journal.pone.0254177 ◽

2021 ◽

Vol 16 (7) ◽

pp. e0254177

Author(s):

Owen Ngalamika ◽

Marie Claire Mukasine ◽

Musonda Kawimbe ◽

Faheema Vally

Keyword(s):

Kaposi Sarcoma ◽

Sub Saharan Africa ◽

Sustained Remission ◽

Hiv Viral Load ◽

Factors Associated ◽

Viral Loads ◽

Cytokines And Chemokines ◽

Immunological Markers ◽

Sub Saharan

Kaposi sarcoma (KS) is an AIDS-defining angio-proliferative malignancy highly prevalent in Sub-Saharan Africa. The main objective of this study was to determine the factors associated with recurrence of HIV-associated KS. We recruited a cohort of individuals on antiretroviral therapy who were in remission for HIV-associated KS after undergoing cytotoxic cancer chemotherapy. Collected variables included sociodemographic and clinical parameters, cytokines and chemokines, HIV viral loads, and CD4 counts. Compared to individuals who had KS recurrence, IL-5 was significantly higher at time of follow-up in individuals who had sustained remission (22.7pg/ml vs. 2.4pg/ml; p = 0.02); IL-6 was significantly higher at baseline and time of follow-up in individuals who had sustained remission, (18.4pg/ml vs. 0pg/ml; p = 0.01) and (18.0pg/ml vs. 0.18pg/ml; p = 0.03) respectively; IP-10 was significantly lower at baseline and at time of follow-up in individuals who had sustained remission, (534pg/ml vs. 920pg/ml; p = 0.04) and (446pg/ml vs.1098pg/ml; p = 0.01) respectively; while HIV viral load was significantly lower at baseline and at time of follow-up in individuals who had sustained remission, (0copies/ml vs. 113copies/ml; p = 0.004) and (0copies/ml vs. 152copies/ml; p = 0.025) respectively. Plasma levels of IL-5, IL-6, and IP-10 are associated with recurrence of HIV-associated KS, while persistently detectable HIV viral loads increase the risk of KS recurrence.

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Feasibility of Rapid Case Ascertainment for Cancer in East Africa: An Investigation of Community-Representative Kaposi Sarcoma in the Era of Antiretroviral Therapy.

10.1101/2021.05.21.21257178 ◽

2021 ◽

Author(s):

Aggrey Semeere ◽

Helen Byakwaga ◽

Miriam Laker-Oketta ◽

Esther Freeman ◽

Naftali Busakhala ◽

...

Keyword(s):

Cancer Research ◽

East Africa ◽

Kaposi Sarcoma ◽

Detailed Examination ◽

Sub Saharan Africa ◽

Case Ascertainment ◽

Community Representative ◽

Resource Limited ◽

Sub Saharan ◽

Record Review

BACKGROUND: Rapid case ascertainment (RCA) refers to the expeditious and detailed examination of patients with a potentially rapidly fatal disease shortly after diagnosis. RCA is frequently performed in resource-rich settings to facilitate cancer research. Despite its utility, RCA is rarely implemented in resource-limited settings and has not been performed for malignancies. One cancer and context that would benefit from RCA in a resource-limited setting is HIV-related Kaposi sarcoma (KS) in sub-Saharan Africa. METHODS: To determine the feasibility of RCA of KS, we searched for all potential newly diagnosed KS among HIV-infected adults attending three community-based facilities in Uganda and Kenya. Searching involved querying of electronic medical records, pathology record review, and notification by clinicians. Upon identification, a team verified eligibility and attempted to locate patients to perform RCA, which included epidemiologic, clinical and laboratory measurements. RESULTS: We identified 593 patients with suspected new KS. Of the 593, 171 were ineligible, mainly because biopsy failed to confirm KS (65%) or KS was not new (30%). Among the 422 remaining, RCA was performed within 1 month for 56% of patients and within 3 months for 65% (95% confidence interval: 59 to 70%). Reasons for not performing RCA included intervening death (47%), inability to contact (44%), refusal/unsuitable to consent (8.3%), and patient re-location (0.7%). CONCLUSIONS: We found that RCA, an important tool for cancer research in resource-rich settings, is feasible for the investigation of community-representative KS in East Africa. Feasibility of RCA for KS suggests feasibility for other cancers in Africa.

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Presentation and Outcomes of Childhood Cancer Patients at Uganda Cancer Institute

Global Pediatric Health ◽

10.1177/2333794x19849749 ◽

2019 ◽

Vol 6 ◽

pp. 2333794X1984974 ◽

Cited By ~ 1

Author(s):

Innocent Mutyaba ◽

Henry R. Wabinga ◽

Jackson Orem ◽

Corey Casper ◽

Warren Phipps

Keyword(s):

Childhood Cancer ◽

Lymphoblastic Leukemia ◽

Kaposi Sarcoma ◽

Sub Saharan Africa ◽

Children With Cancer ◽

Non Hodgkin Lymphoma ◽

Cox's Regression ◽

Sub Saharan ◽

Poor Outcomes ◽

Histological Confirmation

Introduction. Limited data suggest that children with cancer in sub-Saharan Africa have poor survival. We aimed to describe the presentation, treatment outcomes, and factors associated with survival among children with cancer managed at Uganda Cancer Institute. Methods. We retrospectively evaluated patients with childhood cancer (age ≤19 years) from Kyadondo County treated at Uganda Cancer Institute from 2006 to 2009. Cox’s regression and Kaplan-Meier methods were used to study 1-year survival. Results. Among 310 patients studied, median age was 7 years (range = 0.25-19 years), 64% were boys, and 92% had histological confirmation of cancer diagnosis. The commonest diagnoses were Burkitt lymphoma (BL, N = 87), Kaposi sarcoma (KS, N = 68), non-BL non-Hodgkin lymphoma (NHL, N = 32), acute lymphoblastic leukemia (ALL, N = 28), Wilms (N = 28), and Hodgkin disease (HD, N = 20). Advanced disease at diagnosis was common for all cancers (ranging from 45% for KS to 83% for non-BL NHL). Overall, 33.2% abandoned treatment. One-year survival was 68% for HD (95% confidence interval [CI] = 11.3-40.6), 67% for KS (95% CI = 52.1-77.9), 55% for BL (95% CI = 42-66.9), 44% for Wilms (95% CI = 22.5-63), 43% for non-BL NHL (95% CI = 23.3-61.3), and 20% for ALL (95% CI = 6.4-38.7). In univariate and multivariate analysis, anemia and thrombocytopenia were associated with mortality for several cancers. Conclusion. Survival among children with cancer in Uganda is poor. Advanced stage disease and loss to follow-up likely contribute to poor outcomes. Anemia and thrombocytopenia may augment traditional staging methods to provide better prognostic factors in Uganda and warrant further evaluation.

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Identifying Most Effective Treatment Strategies to Control Arterial Hypertension in Sub-Saharan Africa

Case Medical Research ◽

10.31525/ct1-nct04129840 ◽

2019 ◽

Author(s):

Keyword(s):

Arterial Hypertension ◽

Effective Treatment ◽

Treatment Strategies ◽

Sub Saharan Africa ◽

Sub Saharan

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KSHV G protein-coupled receptor inhibits lytic gene transcription in primary-effusion lymphoma cells via p21-mediated inhibition of Cdk2

Blood ◽

10.1182/blood-2005-06-2350 ◽

2006 ◽

Vol 107 (1) ◽

pp. 277-284 ◽

Cited By ~ 32

Author(s):

Mark Cannon ◽

Ethel Cesarman ◽

Chris Boshoff

Keyword(s):

Cell Cycle ◽

Primary Effusion Lymphoma ◽

Kaposi Sarcoma ◽

Vital Role ◽

Tumor Formation ◽

Sub Saharan Africa ◽

Chemical Induction ◽

Independent Manner ◽

Human Genes ◽

Sub Saharan

AbstractKaposi sarcoma (KS) remains the most common AIDS-associated malignancy worldwide. In sub-Saharan Africa especially, this aggressive endothelial-cell tumor is a cause of widespread morbidity and mortality. Infection with Kaposi sarcoma-associated herpesvirus (KSHV) is now known to be an etiologic force behind KS and primary-effusion lymphoma (PEL). Over time, KSHV has pirated many human genes whose products regulate angiogenesis, inflammation, and the cell cycle. One of these, the KSHV vGPCR, is a lytic product that is a constitutively active homolog of the IL-8 receptor. Although it is considered a viral oncogene and causes KS-like lesions in mice, vGPCR expression results in cell-cycle arrest of KSHV-infected PEL cells. In the present study, we show that this arrest is mediated by p21 in a p53-independent manner; the resulting Cdk2 inhibition decreases the efficiency of chemical induction of KSHV lytic transcripts ORF 50 and 26. Importantly, Cdk2 activity is also essential for replication in other human herpesviruses. The ability of vGPCR to delay or abort KSHV replication may explain how despite being a lytic product, this potent signaling molecule has a vital role in tumor formation via its induction of various KS-associated cytokines.

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