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Clinical MedicineAIDS/HIVOncology
Open Access | 
10.1172/jci.insight.167854
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by Caro-Vegas, C. in: JCI | PubMed | Google Scholar
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by
Peng, A.
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1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
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Juarez, A.
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1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
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Silverstein, A.
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1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by Kamiyango, W. in: JCI | PubMed | Google Scholar
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by Villiera, J. in: JCI | PubMed | Google Scholar
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by McAtee, C. in: JCI | PubMed | Google Scholar
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by
Mzikamanda, R.
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1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by Tomoka, T. in: JCI | PubMed | Google Scholar
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by Peckham-Gregory, E. in: JCI | PubMed | Google Scholar
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by
Moorad, R.
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1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by Kovarik, C. in: JCI | PubMed | Google Scholar
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by Campbell, L. in: JCI | PubMed | Google Scholar
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by Mehta, P. in: JCI | PubMed | Google Scholar
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by Kazembe, P. in: JCI | PubMed | Google Scholar
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by
Allen, C.
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1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
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Scheurer, M.
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1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by Ozuah, N. in: JCI | PubMed | Google Scholar
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by Dittmer, D. in: JCI | PubMed | Google Scholar
1UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research, Chapel Hill, North Carolina, USA.
2Texas Children’s Cancer & Hematology Center Global HOPE (Hematology-Oncology Pediatric Excellence) Program Malawi, Lilongwe, Malawi.
3University of Colorado, Department of Pediatrics, Denver, Colorado, USA.
4Baylor College of Medicine (BCM), Department of Pediatrics, Houston, Texas, USA.
5Texas Children’s Hospital Cancer & Hematology Center, Houston, Texas, USA.
6University of North Carolina Project-Malawi, Kamuzu Central Hospital Pathology Laboratory, Lilongwe, Malawi.
7University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8BCM International Pediatric AIDS Initiative Children’s Foundation Tanzania, Mbeya, Tanzania.
9BCM International Pediatric AIDS Initiative Children’s Foundation Malawi, Lilongwe, Malawi.
Address correspondence to: Dirk P. Dittmer, 450 West Drive, CB 7295, Chapel Hill, North Carolina 27599, USA. Phone: 919.966.7962; Email: dirkdittmer@me.com. Or to: Nader Kim El-Mallawany, Texas Medical Center, 1102 Bates Ave., Ste 1025.16, Houston, Texas 77030, USA. Email: Nader.El-Mallawany@bcm.edu.
Authorship note: PNK is deceased.
Find articles by El-Mallawany, N. in: JCI | PubMed | Google Scholar
Authorship note: PNK is deceased.
Published November 22, 2023 - More info
Published in Volume 8, Issue 22 on November 22, 2023
Abstract
BACKGROUND. Kaposi sarcoma (KS) is among the most common childhood cancers in Eastern and Central Africa. Pediatric KS has a distinctive clinical presentation compared with adult KS, which includes a tendency for primary lymph node involvement, a considerable proportion of patients lacking cutaneous lesions, and a potential for fulminant disease. The molecular mechanisms or correlates for these disease features are unknown.
METHODS. This was a cross-sectional study. All cases were confirmed by IHC for KS-associated herpesvirus (KSHV) LANA protein. Baseline blood samples were profiled for HIV and KSHV genome copy numbers by qPCR and secreted cytokines by ELISA. Biopsies were characterized for viral and human transcription, and KSHV genomes were determined when possible.
RESULTS. Seventy participants with pediatric KS were enrolled between June 2013 and August 2019 in Malawi and compared with adult patients with KS. They exhibited high KSHV genome copy numbers and IL-6/IL-10 levels. Four biopsies (16%) had a viral transcription pattern consistent with lytic viral replication.
CONCLUSION. The unique features of pediatric KS may contribute to the specific clinical manifestations and may direct future treatment options.
FUNDING. US National Institutes of Health U54-CA-254569, PO1-CA019014, U54-CA254564, RO1-CA23958.
IntroductionChildhood cancers are infrequent in the US and Europe, with an incidence of 13–16 cases per 100,000 children overall and leukemia being the most common diagnosis. The situation is starkly different in sub-Saharan Africa (SSA), where Kaposi sarcoma-associated herpesvirus (KSHV) is endemic. KSHV is transmitted from mother to child before puberty. In SSA, early-age immune challenges, such as malaria and, more recently, HIV infection, are common. Burkitt lymphoma is the most recognized pediatric viral cancer in SSA, ever since Denis Burkitt described it in 1958 in Uganda and Michael Anthony Epstein and Yvonne Barr associated this endemic childhood neoplasia with Epstein-Barr virus (EBV) (reviewed in ref. 1).
Kaposi sarcoma (KS) emerged as an AIDS-defining disease in the US and Europe in the 1980s (2). It was associated with KSHV in 1994 (3). KSHV, or human herpesvirus 8 (HHV-8), is the etiologic agent of all types of KS. This includes HIV– classic KS and pediatric KS (HIV+ and HIV–) (4). KSHV was endemic in SSA before the emergence of HIV. In SSA, seroconversion peaks before puberty, and a connection with malaria exposure is suspected (5, 6). Since HIV began to spread in SSA, KS has become the most common cancer in males living with HIV in Malawi, Uganda, and other KSHV-endemic countries.
Pediatric KS is one of SSA’s most common childhood cancers, with a median incidence of 67.35 per 100,000 HIV-infected children (7–9), as 90% of the world’s 2 million children living with HIV are in SSA. Many acquired HIV through mother-to-child transmission before the introduction of antiretroviral therapy (ART) to prevent mother-to-child transmission (10). Mother-to-child transmission of KSHV seems less common (11). ART-treated HIV-infected children acquire KSHV infection at the same rate and mount similar serological responses as their HIV-uninfected peers (12). Today, there is better ART coverage in general, including with pregnant women who are living with HIV and who are started on ART to prevent transmission. This decreased the number of children infected with HIV through vertical transmission. Nonetheless, KS still occurs in children and adolescents living with HIV, those who are on ART, and those who are not on ART (13). The effect of the 3-year COVID-induced disruption of HIV care on pediatric KS rates is unclear.
Pediatric KS can have a similar clinical presentation as adult KS, with visceral, oral, and skin lesions (14); however, pediatric KS has additional characteristics (15–17). Many cases present with primary lymph node involvement, some with lymphadenopathy alone, while others present with symptoms seen in KSHV inflammatory cytokine syndrome (KICS) (18). Severe cytopenia is frequent in patients with lymphadenopathic or visceral disease. Currently, there are no universal treatment guidelines for pediatric KS. Treatment recommendations are extrapolated based on adult KS or small retrospective studies (19–22). Our limited knowledge about the molecular pathobiology of pediatric KS (HIV+ and HIV) constitutes a gap in our knowledge that this study aims to close.
Earlier, we proposed a pediatric-specific KS classification (23). Pediatric KS is divided into 4 groups: cutaneous/oral, lymphadenopathic, woody edema, and visceral and/or disseminated cutaneous/oral. It is unknown if these groups represent distinct stages of the disease or are different clinical representations of the same underlying biology. We also observed laboratory correlates of KICS in some children, such as increased levels of KSHV viral load, IL-6, and IL-10 (24–27). Overall, diagnostic options are limited, as most pediatric patients live in low to middle-class countries (LMICs) with a lack of infrastructure and resource constraints. Therefore, studies focusing on pediatric KS are vital to improving the prognosis for these patients.
This report describes a cohort of 70 pediatric patients with KS enrolled between June 2013 and August 2019 at Kamuzu Central Hospital in Lilongwe, Malawi. Clinical and laboratory conditions are compared with adult KS encountered at the same location and time. This comparison highlights the broad spectrum of pediatric KS clinical presentation, typically higher KSHV viral load but a similar transcription profile. We also obtained the first 11 complete KSHV genomes from pediatric KS tumors and showed they cluster with adult KSHV strains from the region. These studies provide biological plausibility to transferring adult treatment regimens, such as pomalidomide and paclitaxel (28, 29), to pediatric KS but point to the need to monitor KSHV and cytokine levels.
ResultsClinical presentation. Seventy participants with pediatric KS were enrolled between June 2013 and August 2019 at Kamuzu Central Hospital in Malawi. Diagnostic biopsies were subjected to LANA staining to confirm the KS diagnosis. All samples, regardless of the biopsy site, skin, lymph, or tonsil, showed robust LANA staining (Figure 1 and Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/jci.insight.167854DS1). HIV status was ascertained per Malawi guidelines using a rapid test or PCR.
Figure 1LANA staining of pediatric KS biopsies. Biopsies from different locations, (A and B) skin, (C and D) tonsil, and (E and F) lymph node, were LANA stained to confirm KS diagnosis. Results for all cases with available blocks for confirmation are presented in Supplemental Figure 1. Scale bar: 50 μm; original magnification at ×20.
The characteristics of the cohort are presented in Table 1. The median age was 6.7 years, and 42% were male. Table 1 also shows the distribution of KS presentations classified as per our earlier schema (23). Class 1A is defined as only having a mild cutaneous or oral KS, while class 1B is a moderate case; 1 (1.4%) and 8 (11.4%) participants fell into these groups, respectively. Class 2 is determined by lymph node involvement. This class represents most cases with 37 participants (52.9%); class 3 is defined as having woody edema, which was seen in 11 (15.7%) cases. Visceral lesion and/or disseminated cutaneous or oral KS was present in 13 (18.6%) cases (Table 1). A total of 50 (71.4%) patients had lymph node involvement, while only 29 (41.4%) had skin lesions. Supplemental Tables 1 and 2 show the clinical characteristics of HIV– (n = 14) and HIV+ (n = 56) participants separately.
Table 1Clinical characteristics of pediatric patients with KS included in this report
Pediatric KS has a different viral presentation than adult KS. To test the hypothesis that pediatric KS presents with a different pathobiology or is most closely associated with a subset of adult KS, fundamental KSHV pathogenesis features, such as viral loads and cytokine profile, were com
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