Anurag Agrawal

False-negative post-18-month confirmatory HIV tests in HIV DNA PCR-positive children: a retrospective analysis.

Objective:The WHO guidelines for children less than 18 months old diagnosed with HIV based on presumptive clinical diagnosis or one virologic test recommend confirmatory HIV antibody testing after 18 months of age. This study describes post-18-month HIV test results following this WHO-recommended confirmatory testing strategy. Design:Case series and retrospective review of routine program data. Methods:Children enrolled at the Baylor Childrens Clinical Center of Excellence, a pediatric and family HIV clinic in Maseru, Lesotho from December 2005 through January 2009 with a positive HIV DNA PCR at less than 18 months of age and HIV rapid test results after 18 months of age were included. Post-18-month confirmatory HIV test results are described. Factors associated with non-positive confirmatory rapid tests were determined using binary logistic regression. Results:Of the 109 children meeting inclusion criteria, 22 (20.2%) had negative and 27 (24.8%) discordant confirmatory rapid tests. Forty-six of these 49 were on antiretroviral therapy (ART). Among these 49, 11 of 24 post-18-month HIV DNA PCRs were negative, whereas nine of 10 post-18-month HIV ELISAs were positive; 29 were definitively and 17 probably HIV-infected, two were uninfected, and one had undetermined status. Only age less than 9 months at ART initiation (odds ratio 4.25, P = 0.002) was associated with non-positive rapid tests. Conclusion:False-negative post-18-month confirmatory rapid tests and HIV DNA PCRs in children on ART are common, associated with early ART initiation, and may lead to inappropriate ART discontinuation and discharge from care of truly HIV-infected children.

Reply to “Childhood cancer in Africa”

To the Editor: We were pleased to see the recent comprehensive and informative review by Kruger et al. [1] entitled Childhood Cancer in Africa. However, we feel compelled to address an important omission that, per Figure 1 from Childhood Cancer in Africa, erroneously indicated there are no pediatric cancer services available in Botswana. In fact, Botswana has an active pediatric hematology/oncology program through partnership between its Ministry of Health (MOH), Baylor College of Medicine (BCM), Texas Children’s Cancer Center (TCCC), Baylor International Pediatric AIDS Initiative (BIPAI), and the Texas Children’s Hospital Global Health Service Corps. Partnership in pediatric HIV care between the MOH and BIPAI began in 1999 when Botswana had the highest adult prevalence of HIV in the world at 35.8% [2]. With assistance from Bristol-Myers Squibb, the Botswana-Baylor Children’s Clinical Centre of Excellence (BBCCOE) was later constructed and opened in 2003 in Gaborone on the campus of PrincessMarina Hospital (PMH), the country’s largest referral hospital. The BBCCOE was the first comprehensive pediatric HIV clinic in sub-Saharan Africa, served as a model for subsequent clinics, and still provides care to thousands of children. Currently, Botswana has the highest antiretroviral therapy coverage for HIV-positive children in subSaharan Africa [3]. With the benefit of the clinical infrastructure, existing partnership with the MOH, and evident need to treat both HIV-associated malignancies and other pediatric hematology/ oncology diagnoses, BIPAI, BCM, and TCCC have had a pediatric hematologist/oncologist in Botswana since 2007. This expanded a previously existing but small pediatric hematology–oncology program at PMH. With a fully nationalized health service, Botswana provides all health care free of charge for citizens including transportation to and from PMH for therapy. The Botswana model concurs with the World Health Organization (WHO) recommendation for universal coverage in low-income countries to promote and sustain health by providing timely access to care [4]. Thus, abandonment of pediatric oncology treatment is nearly non-existent, which differs significantly from rates reported in other resource-limited settings. Chemotherapy is provided free through the government formulary; surgical services are rendered by pediatric surgeons, orthopedic surgeons and neurosurgeons on the PMH staff; and radiation therapy is provided at a local private hospital through a guarantee of payment from the MOH. Additionally, a small number of children are referred to partner institutions in South Africa for interventions unavailable in Botswana. Numerous educational symposia, both in Botswana and in Houston, Texas, have created training opportunities for Batswana healthcare providers and have increased local capacity. A pediatric hematology–oncology fellowship training program is being planned to obviate the need for expatriate pediatric hematologist/oncologists. The program is also making significant scholarly contributions to the literature [5]. In their conclusion, Kruger et al. [1] suggest partnering with the established framework of the HIV/AIDS infrastructure in Africa to address pediatric cancer care. Botswana serves as a striking example of the feasibility and success of such collaboration.

Exhaled breath condensate metabolome clusters for endotype discovery in asthma

BackgroundAsthma is a complex, heterogeneous disorder with similar presenting symptoms but with varying underlying pathologies. Exhaled breath condensate (EBC) is a relatively unexplored matrix which reflects the signatures of respiratory epithelium, but is difficult to normalize for dilution.MethodsHere we explored whether internally normalized global NMR spectrum patterns, combined with machine learning, could be useful for diagnostics or endotype discovery. Nuclear magnetic resonance (NMR) spectroscopy of EBC was performed in 89 asthmatic subjects from a prospective cohort and 20 healthy controls. A random forest classifier was built to differentiate between asthmatics and healthy controls. Clustering of the spectra was done using k-means to identify potential endotypes.ResultsNMR spectra of the EBC could differentiate between asthmatics and healthy controls with 80% sensitivity and 75% specificity. Unsupervised clustering within the asthma group resulted in three clusters (n = 41,11, and 9). Cluster 1 patients had lower long-term exacerbation scores, when compared with other two clusters. Cluster 3 patients had lower blood eosinophils and higher neutrophils, when compared with other two clusters with a strong family history of asthma.ConclusionAsthma clusters derived from NMR spectra of EBC show important clinical and chemical differences, suggesting this as a useful tool in asthma endotype-discovery.

Establishing a Pediatric Hematology-Oncology Program in Botswana

Purpose Annually, 300,000 children are diagnosed with cancer, and the majority of these children live in low- and middle-income countries (LMICs). Currently, there is incomplete information on pediatric cancer incidence, diagnosis distribution, and treatment outcomes in Africa. Since 2007, a pediatric hematology-oncology program has been operating in Botswana through a partnership between the Botswana government, Baylor College of Medicine, and Texas Children’s Hospital. Methods To better understand patient characteristics and outcomes at Botswana’s only pediatric cancer program, a hospital-based data base—the Botswana Pediatric Oncology Database—was established in 2014. Children younger than 18 years of age at the time of diagnosis who presented between 2008 and 2015 were included. Data for this study were extracted in February 2016. Results Of the 240 potential enrollees, 185 (77%) children met eligibility for this study. The median age was 6.4 years, and 50.8% were male. Leukemia was the most common malignancy representing 18.9% of the cohort and 88.1% of the total cohort had a histopathologic diagnosis. HIV seropositivity was confirmed in 13.5%. The 2-year overall survival of all pediatric cancer diagnoses was 52.4%. Abandonment of treatment occurred in 3.8% of patients. Conclusion In the first 9 years of the program, capacity has been developed through a longstanding partnership between Botswana and Baylor College of Medicine/Texas Children’s Hospital that has led to children receiving care for cancer and blood disorders. Although continued improvements are necessary, outcomes to date indicate that children with cancer in Botswana can be successfully diagnosed and treated.

Proposal of a Risk-Stratification Platform to Address Distinct Clinical Features of Pediatric Kaposi Sarcoma in Lilongwe, Malawi

Prior studies suggest that the clinical features associated with survival in childhood KS are distinct from those in adults.6-14 In our retrospective study of factors associated with event-free survival (EFS) and overall survival (OS) in pediatric KS, multivariable analysis demonstrated that visceral disease and disseminated skin/oral presentation (defined as ≥ 20 hyperpigmented lesions in a widespread distribution) were independent risk factors for death and inability to achieve EFS with a minimally myelosuppressive regimen that contains bleomycin and vincristine (BV), which is commonly available even in low-income settings.12 Patients with woody edema had low EFS but did not experience increased mortality.12 Lymphadenopathic involvement in children was associated with the highest rates of long-term complete remission (CR).12