Browsing by Author "Malone, LaShaunda"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    CD81 T Cells Provide an Immunologic Signature of Tuberculosis in Young Children
    (American Thoracic Society, 2011) Lancioni, Christina; Nyendak, Mellisa; Sarah Zalwango, Sarah Kiguli; Mori, Tomi; Mayanja-Kizza, Harriet; Balyejusa, Stephen; Null, Megan; Baseke, Joy; Mulindwa, Deo; Byrd, Laura; Swarbrick, Gwendolyn; Scott, Christine; Johnson, Denise F.; Malone, LaShaunda; Mudido-Musoke, Philipa; Boom, Henry; Lewinsohn, David M.; Lewinsohn, Deborah A.
    Mycobacterium tuberculosis (Mtb), the etiology of tuberculosis (TB), causes over 9 million cases of disease and 1.7 million deaths annually (1). The only available vaccine to prevent TB, bacillus Calmette-Gue´ rin, offers little protection against the most common disease manifestations (2) and efforts to develop an improved vaccine are hampered by poor understanding of immunologic events that occur after Mtb exposure. Scientific studies of immunologic responses to initial Mtb infection are difficult because most individuals living in TB-endemic settings have experienced multiple Mtb exposures. Young children, however, suffer disproportionately after exposure to Mtb, because they are at substantial risk for developing TB after primary infection (3–5). Therefore, young children with TB offer a valuable window into the human immune response to primary Mtb infection.
  • Thumbnail Image
    Item
    Contact Investigation for Active Tuberculosis Among Child Contacts in Uganda
    (Oxford University Press, 2013) Jaganath, Devan; Zalwango, Sarah; Okware, Brenda; Nsereko, Mary; Kisingo, Hussein; Malone, LaShaunda; Lancioni, Christina; Okwera, Alphonse; Joloba, Moses; Mayanja-Kizza, Harriet; Boom, Henry; Stein, Catherine; Mupere, Ezekiel
    Background. Tuberculosis is a large source of morbidity and mortality among children. However, limited studies characterize childhood tuberculosis disease, and contact investigation is rarely implemented in high-burden settings. In one of the largest pediatric tuberculosis contact investigation studies in a resource-limited setting, we assessed the yield of contact tracing on childhood tuberculosis and indicators for disease progression in Uganda. Methods. Child contacts aged <15 years in Kampala, Uganda, were enrolled from July 2002 to June 2009 and evaluated for tuberculosis disease via clinical, radiographic, and laboratory methods for up to 24 months. Results. Seven hundred sixty-one child contacts were included in the analysis. Prevalence of tuberculosis in our child population was 10%, of which 71% were culture-confirmed positive. There were no cases of disseminated tuberculosis, and 483 of 490 children (99%) started on isoniazid preventative therapy did not develop disease. Multivariable testing suggested risk factors including human immunodeficiency virus (HIV) status (odds ratio [OR], 7.90; P < .001), and baseline positive tuberculin skin test (OR, 2.21; P = .03); BCG vaccination was particularly protective, especially among children aged ≤5 years (OR, 0.23; P < .001). Adult index characteristics such as sex, HIV status, and extent or severity of disease were not associated with childhood disease. Conclusions. Contact tracing for children in high-burden settings is able to identify a large percentage of culture-confirmed positive tuberculosis cases before dissemination of disease, while suggesting factors for disease progression to identify who may benefit from targeted screening.
  • Thumbnail Image
    Item
    A prospective validation of a Clinical Algorithm to detect Tuberculosis in child contacts
    (American Thoracic Society, 2018) Zalwango, Sarah; Malone, LaShaunda; Stein, Catherine; Quinn, Frederick; Chakraburty, Srijita; Shen, Ye; Handel, Andreas; Martinez, Leonardo
    Over 60% of pediatric tuberculosis cases are undetected by healthcare services in low-income settings (1). Untreated children with tuberculosis have fatality rates of .20%, reaching above 40% in children ,5 years old (2). Specific, effective, and validated interventions to increase case detection in children are urgently needed.
  • Thumbnail Image
    Item
    Resistance to TST/IGRA conversion in Uganda: Heritability and Genome-Wide 2 Association Study
    (EBioMedicine, 2021) McHenry, Michael L.; Benchek, Penelope; Malone, LaShaunda; Nsereko, Mary; Mayanja-Kizza, Harriet; Boom, W. Henry; Williams, Scott M.; Hawn, Thomas R.; Stein, Catherine M.
    Pulmonary tuberculosis (TB) is one of the most deadly pathogens on earth. However, the majority of people have resistance to active disease. Further, some individuals, termed resisters (RSTRs), do not develop traditional latent tuberculosis (LTBI). The RSTR phenotype is important for understanding pathogenesis and preventing TB. The host genetic underpinnings of RSTR are largely understudied. Methods: In a cohort of 908 Ugandan subjects with genome-wide data on single nucleotide polymorphisms, we assessed the heritability of the RSTR phenotype and other TB phenotypes using restricted maximum likelihood estimation (REML). We then used a subset of 263 RSTR and LTBI subjects with high quality phenotyping and long-term follow-up to identify DNA variants genome-wide associated with the RSTR phenotype relative to LTBI subjects in a case- control GWAS design, and annotated and enriched these variants to better understand their role in TB pathogenesis. Results: The heritability of the TB outcomes was very high, at 55% for TB vs. LTBI and 50.4% for RSTR vs. LTBI among HIV- subjects, controlling for age and sex. We identified 27 loci associated with the RSTR phenotype (P<5e-05) and our annotation and enrichment analyses suggest an important regulatory role for many of them. Interpretation: The heritability results show that the genetic contribution to variation in TB outcomes is very high and our GWAS results highlight variants that may play an important role in resistance to infection as well as TB pathogenesis as a whole.
  • Thumbnail Image
    Item
    Secondary Attack Rate of Tuberculosis in Urban Households in Kampala, Uganda
    (PLoS ONE, 2011) Whalen, Christopher C.; Zalwango, Sarah; Chiunda, Allan; Malone, LaShaunda; Eisenach, Kathleen; Joloba, Moses; Boom, W. Henry; Mugerwa, Roy
    Tuberculosis is an ancient disease that continues to threaten individual and public health today, especially in sub-Saharan Africa. Current surveillance systems describe general risk of tuberculosis in a population but do not characterize the risk to an individual following exposure to an infectious case. Methods: In a study of household contacts of infectious tuberculosis cases (n = 1918) and a community survey of tuberculosis infection (N = 1179) in Kampala, Uganda, we estimated the secondary attack rate for tuberculosis disease and tuberculosis infection. The ratio of these rates is the likelihood of progressive primary disease after recent household infection. Results: The secondary attack rate for tuberculosis disease was 3.0% (95% confidence interval: 2.2, 3.8). The overall secondary attack rate for tuberculosis infection was 47.4 (95% confidence interval: 44.3, 50.6) and did not vary widely with age, HIV status or BCG vaccination. The risk for progressive primary disease was highest among the young or HIV infected and was reduced by BCG vaccination. Conclusions: Early case detection and treatment may limit household transmission of M. tuberculosis. Household members at high risk for disease should be protected through vaccination or treatment of latent tuberculosis infection.
  • Thumbnail Image
    Item
    Wasting among Uganda men with pulmonary tuberculosis is associated with linear regain in lean tissue mass during and after treatment in contrast to women with wasting who regain fat tissue mass: prospective cohort study
    (Bio med central, 2014) Malone, LaShaunda; Zalwango, Sarah; Okwera, Alphonse; Nsereko, Mary; Tisch, Daniel J; Parraga, Isabel M; Stein, Catherine M.; Mugerwa, Roy; Boom, Henry W.; Mayanja, Harriet K; Whalen, Christopher C; Mupere, Ezekiel
    Background: Nutritional changes during and after tuberculosis treatment have not been well described. We therefore determined the effect of wasting on rate of mean change in lean tissue and fat mass as measured by bioelectrical impedance analysis (BIA), and mean change in body mass index (BMI) during and after tuberculosis treatment. Methods: In a prospective cohort study of 717 adult patients, BMI and height-normalized indices of lean tissue (LMI) and fat mass (FMI) as measured by BIA were assessed at baseline, 3, 12, and 24 months. Results: Men with wasting at baseline regained LMI at a greater rate than FMI (4.55 kg/m2 (95% confidence interval (CI): 1.26, 7.83 versus 3.16 (95% CI: 0.80, 5.52)) per month, respectively during initial tuberculosis therapy. In contrast, women with wasting regained FMI at greater rate than LMI (3.55 kg/m2 (95% CI: 0.40, 6.70) versus 2.07 (95% CI: -0.74, 4.88)), respectively. Men with wasting regained BMI at a rate of 6.45 kg/m2 (95% CI: 3.02, 9.87) in the first three months whereas women, had a rate of 3.30 kg/m2 (95% CI: -0.11, 6.72). There were minimal changes in body composition after month 3 and during months 12 to 24. Conclusion: Wasted tuberculosis patients regain weight with treatment but the type of gain differs by gender and patients may remain underweight after the initial phase of treatment