NRU :: Browsing by Author "Whalen, Christopher C."

Browsing by Author "Whalen, Christopher C."

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Assessing a transmission network of Mycobacterium tuberculosis in an African city using single nucleotide polymorphism threshold analysis
(MicrobiologyOpen, 2021) Yassine, Edriss; Galiwango, Ronald; Ssengooba, Willy; Ashaba, Fred; Joloba, Moses L.; Zalwango, Sarah; Whalen, Christopher C.; Quinn, Frederick
Tuberculosis (TB) is the leading cause of death in humans by a single infectious agent worldwide with approximately two billion humans latently infected with the bacterium Mycobacterium tuberculosis. Currently, the accepted method for controlling the disease is Tuberculosis Directly Observed Treatment Shortcourse (TB-DOTS). This program is not preventative and individuals may transmit disease before diagnosis, thus better understanding of disease transmission is essential. Using whole-genome sequencing and single nucleotide polymorphism analysis, we analyzed genomes of 145 M. tuberculosis clinical isolates from active TB cases from the Rubaga Division of Kampala, Uganda. We established that these isolates grouped into M. tuberculosis complex (MTBC) lineages 1, 2, 3, and 4, with the most isolates grouping into lineage 4. Possible transmission pairs containing ≤12 SNPs were identified in lineages 1, 3, and 4 with the prevailing transmission in lineages 3 and 4. Furthermore, investigating DNA codon changes as a result of specific SNPs in prominent virulence genes including plcA and plcB could indicate potentially important modifications in protein function. Incorporating this analysis with corresponding epidemiological data may provide a blueprint for the integration of public health interventions to decrease TB transmission in a region.
Association between tuberculosis in men and social network structure in Kampala, Uganda
(BMC infectious diseases, 2021) Miller, Paige B.; Zalwango, Sarah; Galiwango, Ronald; Kakaire, Robert; Sekandi, Juliet; Steinbaum, Lauren; Drake, John M.; Whalen, Christopher C.; Kiwanuka, Noah
Globally, tuberculosis disease (TB) is more common among males than females. Recent research proposes that differences in social mixing by sex could alter infection patterns in TB. We examine evidence for two mechanisms by which social-mixing could increase men’s contact rates with TB cases. First, men could be positioned in social networks such that they contact more people or social groups. Second, preferential mixing by sex could prime men to have more exposure to TB cases. Methods: We compared the networks of male and female TB cases and healthy matched controls living in Kampala, Uganda. Specifically, we estimated their positions in social networks (network distance to TB cases, degree, betweenness, and closeness) and assortativity patterns (mixing with adult men, women, and children inside and outside the household). Results: The observed network consisted of 11,840 individuals. There were few differences in estimates of node position by sex. We found distinct mixing patterns by sex and TB disease status including that TB cases have proportionally more adult male contacts and fewer contacts with children. Conclusions: This analysis used a network approach to study how social mixing patterns are associated with TB disease. Understanding these mechanisms may have implications for designing targeted intervention strategies in high-burden populations.
Bioinformatics mentorship in a resource limited setting
(Briefings in Bioinformatics, 2021) Jjingo, Daudi; Mboowa, Gerald; Sserwadda, Ivan; Kakaire, Robert; Kiberu, Davis; Amujal, Marion; Galiwango, Ronald; Kateete, David; Joloba, Moses; Whalen, Christopher C.
The two recent simultaneous developments of high-throughput sequencing and increased computational power have brought bioinformatics to the forefront as an important tool for effective and efficient biomedical research. Consequently, there have been multiple approaches to developing bioinformatics skills. In resource rich environments, it has been possible to develop and implement formal fully accredited graduate degree training programs in bioinformatics. In resource limited settings with a paucity of expert bioinformaticians, infrastructure and financial resources, the task has been approached by delivering short courses on bioinformatics—lasting only a few days to a couple of weeks. Alternatively, courses are offered online, usually over a period of a few months. These approaches are limited by both the lack of sustained in-person trainer–trainee interactions, which is a key part of quality mentorships and short durations which constrain the amount of learning that can be achieved.
Defining adequate contact for transmission of Mycobacterium tuberculosis in an African urban environment
(BMC public health, 2020) Castellanos, María Eugenia; Zalwango, Sarah; Kakaire, Robert; Ebell, Mark H.; Dobbin, Kevin K.; Sekandi, Juliet; Kiwanuka, Noah; Whalen, Christopher C.
The risk of infection from respiratory pathogens increases according to the contact rate between the infectious case and susceptible contact, but the definition of adequate contact for transmission is not standard. In this study we aimed to identify factors that can explain the level of contact between tuberculosis cases and their social networks in an African urban environment. Methods: This was a cross-sectional study conducted in Kampala, Uganda from 2013 to 2017. We carried out an exploratory factor analysis (EFA) in social network data from tuberculosis cases and their contacts. We evaluated the factorability of the data to EFA using the Kaiser-Meyer-Olkin Measure of Sampling Adequacy (KMO). We used principal axis factoring with oblique rotation to extract and rotate the factors, then we calculated factor scores for each using the weighted sum scores method. We assessed construct validity of the factors by associating the factors with other variables related to social mixing. Results: Tuberculosis cases (N = 120) listed their encounters with 1154 members of their social networks. Two factors were identified, the first named “Setting” captured 61% of the variance whereas the second, named ‘Relationship’ captured 21%. Median scores for the setting and relationship factors were 10.2 (IQR 7.0, 13.6) and 7.7 (IQR 6.4, 10.1) respectively. Setting and Relationship scores varied according to the age, gender, and nature of the relationship among tuberculosis cases and their contacts. Family members had a higher median setting score (13.8, IQR 11.6, 15.7) than non-family members (7.2, IQR 6.2, 9.4). The median relationship score in family members (9.9, IQR 7.6, 11.5) was also higher than in non-family members (6.9, IQR 5.6, 8.1). For both factors, household contacts had higher scores than extra-household contacts (p < .0001). Contacts of male cases had a lower setting score as opposed to contacts of female cases. In contrast, contacts of male and female cases had similar relationship scores. Conclusions: In this large cross-sectional study from an urban African setting, we identified two factors that can assess adequate contact between tuberculosis cases and their social network members. These findings also confirm the complexity and heterogeneity of social mixing.
Defining an intermediate category of tuberculin skin test: A mixture model analysis of two high-risk populations from Kampala, Uganda
(Creative Commons Attribution License, 2021) Woldu, Henok G.; Zalwango, Sarah; Martinez, Leonardo; Castellanos, Maria Eugenia; Kakaire, Robert; Sekandi, Juliet N.; Kiwanuka, Noah; Whalen, Christopher C.
One principle of tuberculosis control is to prevent the development of tuberculosis disease by treating individuals with latent tuberculosis infection. The diagnosis of latent infection using the tuberculin skin test is not straightforward because of concerns about immunologic cross reactivity with the Bacille Calmette-Guerin (BCG) vaccine and environmental mycobacteria. To parse the effects of BCG vaccine and environmental mycobacteria on the tuberculin skin test, we estimated the frequency distribution of skin test results in two divisions of Kampala, Uganda, ten years apart. We then used mixture models to estimate parameters for underlying distributions and defined clinically meaningful criteria for latent infection, including an indeterminate category. Using percentiles of two underlying normal distributions, we defined two skin test readings to demarcate three ranges. Values of 10 mm or greater contained 90% of individuals with latent infection; values less than 7.2 mm contained 80% of individuals without infection. Contacts with values between 7.2 and 10 mm fell into an indeterminate zone where it was not possible to assign infection. We conclude that systematic tuberculin skin test surveys within populations at risk, combined with mixture model analysis, may be a reproducible, evidence-based approach to define meaningful criteria for latent tuberculosis infection.
Dose-Modified Oral Chemotherapy in the Treatment of AIDS-Related Non-Hodgkin’s Lymphoma in East Africa
(2009-05-26) Mwanda, Walter O; Orem, Jackson; Fu, Pingfu; Banura, Cecilia; Kakembo, Joweria; Onyango, Caren Auma; Ness, Anne; Reynolds, Sherrie; Johnson, John L.; Subbiah, Vivek; Bako, Jacob; Wabinga, Henry; Abdallah, Fatuma K.; Meyerson, Howard J.; Whalen, Christopher C.; Lederman, Michael M.; Black, Jodi; Ayers, Leona W.; Ayers, Leona W.; Katongole-Mbidde, Edward; C., Scot; Remick, Scot C.
Purpose Africa is burdened by the AIDS epidemic and attendant increase in HIV/AIDS-related malignancies. Pragmatic approaches to therapeutic intervention could be of great value. Dose-modified oral chemotherapy for AIDS-related non-Hodgkin's lymphoma is one such approach. Patients and Methods The oral regimen consisted of lomustine 50 mg/m2 on day 1 (cycle 1 only), etoposide 100 mg/m2 on days 1 to 3, and cyclophosphamide/procarbazine 50 mg/m2 each on days 22 to 26 at 6-week intervals (one cycle) for two total cycles in HIV-infected patients with biopsy-proven non-Hodgkin's lymphoma. Results Forty-nine patients (21 in Uganda and 28 in Kenya) were treated. The majority of patients were female (59%) and had a poor performance status (63%); 69% of patients had advanced-stage disease; and 18 patients (37%) had access to antiretroviral therapy. In total, 79.5 cycles of therapy were administered. The regimen was well tolerated, had modest effects (decline) on CD4+ lymphocyte counts (P = .077), and had negligible effects on HIV-1 viral replication. Four febrile neutropenia episodes and three treatment-related deaths (6% mortality rate) occurred. The overall objective response rate was 78% (95% CI, 62% to 88%); median follow-up time was 8.2 months (range, 0.1 to 71 months); median event-free and overall survival times were 7.9 months (95% CI, 3.3 to 13.0 months) and 12.3 months (95% CI, 4.9 to 32.4 months), respectively; and 33% of patients survived 5 years. Conclusion Dose-modified oral chemotherapy is efficacious, has comparable outcome to that in the United States in the pre–highly active antiretroviral therapy setting, has an acceptable safety profile, and is pragmatic in sub-Saharan Africa. The international collaboration has been highly successful, and subsequent projects should focus on strategies to optimize combination antiretroviral therapy and chemotherapy and follow-up tissue correlative studies.
Excess Risk of Tuberculosis Infection Among Extra-household Contacts of Tuberculosis Cases in an African City
(Clinical Infectious Diseases, 2021) Kakaire, Robert; Kiwanuka, Noah; Zalwango, Sarah; Sekandi, Juliet N.; Quach, Trang Ho Thu; Castellanos, Maria Eugenia; Quinn, Frederick; Whalen, Christopher C.
Although households of tuberculosis (TB) cases represent a setting for intense transmission of Mycobacterium tuberculosis, household exposure accounts for <20% of transmission within a community. The aim of this study was to estimate excess risk of M. tuberculosis infection among household and extra-household contacts of index cases. Methods. We performed a cross-sectional study in Kampala, Uganda, to delineate social networks of TB cases and matched controls without TB. We estimated the age-stratified prevalence difference of TB infection between case and control networks, partitioned as household and extra-household contacts. Results. We enrolled 123 index cases, 124 index controls, and 2415 first-degree network contacts. The prevalence of infection was highest among household contacts of cases (61.5%), lowest among household contacts of controls (25.2%), and intermediary among extra-household TB contacts (44.9%) and extra-household control contacts (41.2%). The age-adjusted prevalence difference between extra-household contacts of cases and their controls was 5.4%. The prevalence of infection was similar among the majority of extra-household case contacts and corresponding controls (47%). Conclusions. Most first-degree social network members of TB cases do not have adequate contact with the index case to experience additional risk for infection, but appear instead to acquire infection through unrecognized exposures with infectious cases in the community.
Four Degrees of Separation: Social Contacts and Health Providers Influence the Steps to Final Diagnosis of Active Tuberculosis Patients in Urban Uganda
(BMC infectious diseases, 2015) Sekandi, Juliet N.; Zalwango, Sarah; Martinez, Leonardo; Handel, Andreas; Kakaire, Robert; Nkwata, Allan K.; Ezeamama, Amara E.; Kiwanuka, Noah; Whalen, Christopher C.
Delay in tuberculosis (TB) diagnosis adversely affects patients’ outcomes and prolongs transmission in the community. The influence of social contacts on steps taken by active pulmonary TB patients to seek a diagnosis has not been well examined. Methods: A retrospective study design was use to enroll TB patients on treatment for 3 months or less and aged ≥18 years from 3 public clinics in Kampala, Uganda, from March to July 2014. Social network analysis was used to collect information about social contacts and health providers visited by patients to measure the number of steps and time between onset of symptoms and final diagnosis of TB. Results: Of 294 TB patients, 58 % were male and median age was 30 (IQR: 24–38) years. The median number of steps was 4 (IQR: 3, 7) corresponding to 70 (IQR: 28,140) days to diagnosis. New patients had more steps and time to diagnosis compared retreatment patients (5 vs. 3, P < 0.0001; 84 vs. 46 days P < 0.0001). Fifty-eight percent of patients first contacted persons in their social network. The first step to initiate seeking care accounted for 41 % of the patients’ time to diagnosis while visits to non-TB providers and TB providers (without a TB diagnosis) accounted for 34 % and 11 % respectively. New TB patients vs. retreatment (HR: 0.66, 95 % CI; 1.11, 1.99), those who first contacted a non-TB health provider vs. contacting social network (HR: 0.72 95 % CI; 0.55, 0.95) and HIV seronegative vs. seropositive patients (HR: 0.70, 95 % CI; 0.53, 0.92) had a significantly lower likelihood of a timely final diagnosis. Conclusions: There were four degrees of separation between the onset of symptoms in a TB patient and a final diagnosis. Both social and provider networks of patients influenced the diagnostic pathways. Most delays occurred in the first step which represents decisions to seek help, and through interactions with non-TB health providers. TB control programs should strengthen education and active screening in the community and in health care settings to ensure timely diagnosis of TB.
Genome Scan of M. tuberculosis Infection and Disease in Ugandans
(PLoS ONE, 2018) Stein, Catherine M.; Zalwango, Sarah; Malone, LaShaunda L.; Won1, Sungho; Mayanja- Kizza, Harriet; Mugerwa, Roy D.; Leontiev, Dmitry V.; Thompson, Cheryl L.; Cartier, Kevin C.; Elston, Robert C.; Iyengar, Sudha K.; Boom, Henry; Whalen, Christopher C.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is an enduring public health problem globally, particularly in sub-Saharan Africa. Several studies have suggested a role for host genetic susceptibility in increased risk for TB but results across studies have been equivocal. As part of a household contact study of Mtb infection and disease in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB, by studying three phenotypes. First, we analyzed culture confirmed TB disease compared to latent Mtb infection (LTBI) or lack of Mtb infection. Second, we analyzed resistance to Mtb infection in the face of continuous exposure, defined by a persistently negative tuberculin skin test (PTST-); this outcome was contrasted to LTBI. Third, we analyzed an intermediate phenotype, tumor necrosis factor-alpha (TNFa) expression in response to soluble Mtb ligands enriched with molecules secreted from Mtb (culture filtrate). We conducted a full microsatellite genome scan, using genotypes generated by the Center for Medical Genetics at Marshfield. Multipoint model-free linkage analysis was conducted using an extension of the Haseman-Elston regression model that includes half sibling pairs, and HIV status was included as a covariate in the model. The analysis included 803 individuals from 193 pedigrees, comprising 258 full sibling pairs and 175 half sibling pairs. Suggestive linkage (p,1023) was observed on chromosomes 2q21-2q24 and 5p13-5q22 for PTST-, and on chromosome 7p22-7p21 for TB; these findings for PTST- are novel and the chromosome 7 region contains the IL6 gene. In addition, we replicated recent linkage findings on chromosome 20q13 for TB (p = 0.002). We also observed linkage at the nominal a = 0.05 threshold to a number of promising candidate genes, SLC11A1 (PTST- p = 0.02), IL-1 complex (TB p = 0.01), IL12BR2 (TNFa p = 0.006), IL12A (TB p = 0.02) and IFNGR2 (TNFa p = 0.002). These results confirm not only that genetic factors influence the interaction between humans and Mtb but more importantly that they differ according to the outcome of that interaction: exposure but no infection, infection without progression to disease, or progression of infection to disease. Many of the genetic factors for each of these stages are part of the innate immune system.
Heritability Analysis of Cytokines as Intermediate Phenotypes of Tuberculosis
(The Journal of infectious diseases, 2003) Stein, Catherine M.; Guwatudde, David; Nakakeeto, Margaret; Peters, Pierre; Elston, Robert C.; Tiwari, Hemant K.; Mugerwa, Roy; Whalen, Christopher C.
Numerous studies have provided support for genetic susceptibility to tuberculosis (TB); however, heterogeneity in disease expression has hampered previous genetic studies. The purpose of this work was to investigate possible intermediate phenotypes for TB. A set of cytokine profiles, including antigen-stimulated whole-blood assays for interferon (IFN)–g, tumor necrosis factor (TNF)–a, transforming growth factor (TGF)–b, and the ratio of IFN to TNF, were analyzed in 177 pedigrees from a community in Uganda with a high prevalence of TB. The heritability of these variables was estimated after adjustment for covariates, and TNF-a, in particular, had an estimated heritability of 68%. A principal component analysis of IFN-g, TNF-a, and TGF-b reflected the immunologic model of TB. In this analysis, the first component explained 138% of the variation in the data. This analysis illustrates the value of such intermediate phenotypes in mapping susceptibility loci for TB and demonstrates that this area deserves further research.
Infectiousness of HIV-Seropositive Patients with Tuberculosis in a High-Burden African Setting
(PloS one, 2016) Martinez, Leonardo; Sekandi, Juliet N.; Castellanos, Maria E.; Zalwango, Sarah; Whalen, Christopher C.
Policy recommendations on contact investigation of HIV-seropositive patients with tuberculosis have changed several times. Current epidemiologic evidence informing these recommendations is considered low quality, and few large studies investigating the infectiousness of HIV-seropositive and -seronegative index cases have been performed in sub-Saharan Africa. Objectives: We assessed the infectiousness of HIV-seropositive and -seronegative patients with tuberculosis to their household contacts and examined potential modifiers of this relationship. Methods: Adults suffering from their first episode of pulmonary tuberculosis were identified in Kampala, Uganda. Field workers visited index households and enrolled consenting household contacts. Latent tuberculosis infection was measured through tuberculin skin testing, and relative risks were calculated using modified Poisson regression models. Standard assessments of interaction between latent tuberculosis infection, the HIV serostatus of index cases, and other variables were performed.
Innate and Adaptive Immune Responses during Acute M. tuberculosis Infection in Adult Household Contacts in Kampala, Uganda
(The American journal of tropical medicine and hygiene, 2011) Mahan, C. Scott; Zalwango, Sarah; Thiel, Bonnie A.; Malone, LaShaunda L.; Chervenak, Keith A.; Baseke, Joy; Dobbs, Dennis; Stein, Catherine M.; Mayanja, Harriet; Joloba, Moses; Whalen, Christopher C.; Boom, W. Henry
Contacts of active pulmonary tuberculosis (TB) patients are at risk for Mycobacterium tuberculosis (MTB) infection. Because most infections are controlled, studies during MTB infection provide insight into protective immunity. We compared immune responses of adult household contacts that did and did not convert the tuberculin skin test (TST). Innate and adaptive immune responses were measured by whole blood assay. Responses of TST converters (TSTC) were compared with persistently TST negative contacts (PTST–) and contacts who were TST+ at baseline (TST+). TLR-2, TLR-4, and IFN-gR responses to IFN-g did not differ between the groups, nor did gd T cell responses. T cell responses to MTB antigens differed markedly among TSTC, PTST–, and TST+ contacts. Thus, no differences in innate responses were found among the three household contact groups. However, adaptive T cell responses to MTB antigens did differ before and during MTB infection among PTST–, TSTC, and TST+ contacts.
Lean Tissue Mass Wasting is Associated With Increased Risk of Mortality Among Women With Pulmonary Tuberculosis in Urban Uganda
(Elsevier Inc., 2012) Mupere, Ezekiel; Malone, Lashaunda; Zalwango, Sarah; Chiunda, Allan; Okwera, Alphonse; Parraga, Isabel; Stein, Catherine M.; Tisch, Daniel J.; Mugerwa, Roy; Boom, W. Henry; Mayanja, Harriet; Whalen, Christopher C.
OBJECTIVES: We assessed the impact of wasting on survival in patients with tuberculosis by using a precise height-normalized lean tissue mass index (LMI) estimated by bioelectrical impedance analysis and body mass index (BMI). METHODS: In a retrospective cohort study, 747 adult pulmonary patients with tuberculosis who were screened for HIV and nutritional status were followed for survival. RESULTS: Of 747 patients, 310 had baseline wasting by BMI (kg/m2) and 103 by LMI (kg/m2). Total deaths were 105. Among men with reduced BMI, risk of death was 70% greater (hazard ratio [HR] 1.7, 95% confidence interval [95% CI] 1.03–2.81) than in men with normal BMI. Survival did not differ by LMI among men (HR 1.1; 95% CI 0.5–2.9). In women, both the BMI and LMI were associated with survival. Among women with reduced BMI, risk of death was 80% greater (HR 1.8; 95% CI 0.9–3.5) than in women with normal BMI; risk of death was 5-fold greater (HR 5.0; 95% CI 1.6–15.9) for women with low LMI compared with women with normal LMI. CONCLUSIONS: Wasting assessed by reduced BMI is associated with an increased risk for death among both men and women whereas reduced LMI is among women with tuberculosis.
Linkage and association analysis of candidate genes for TB and TNFa cytokine expression: evidence for association with IFNGR1, IL-10, and TNF receptor 1 genes
(Springer, 2007) Stein, Catherine M.; Zalwango, Sarah; Chiunda, Allan B.; Millard, Christopher; Leontiev, Dmitry V.; Horvath, Amanda L.; Cartier, Kevin C.; Chervenak, Keith; Boom, W. Henry; Elston, Robert C.; Mugerwa, Roy D.; Whalen, Christopher C.; Iyengar, Sudha K.
Tuberculosis (TB) is a growing public health threat globally and several studies suggest a role of host genetic susceptibility in increased TB risk. As part of a household contact study in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB by developing an intermediate phenotype model for TB susceptibility, analyzing levels of tumor necrosis factor-a (TNFa) in response to culture filtrate as the phenotype. In the present study, we analyzed candidate genes related to TNFa regulation and found that interleukin (IL)-10, interferon-gamma receptor 1 (IFNGR1), and TNFa receptor 1 (TNFR1) genes were linked and associated to both TB and TNFa. We also show that these associations are with progression to active disease and not susceptibility to latent infection. This is the first report of an association between TB and TNFR1 in a human population and our findings for IL-10 and IFNGR1 replicate previous findings. By observing pleiotropic effects on both phenotypes, we show construct validity of our intermediate phenotype model, which enables the characterization of the role of these genetic polymorphisms on TB pathogenesis. This study further illustrates the utility of such a model for disentangling complex traits.
Mycobacterium tuberculosis Microbiologic and Clinical Treatment Outcomes in a Randomized Trial of Immediate versus CD4+ -Initiated Antiretroviral Therapy in HIV-Infected Adults with a High CD4+ Cell Count
(Clinical infectious diseases, 2010) Chamie, Gabriel; Charlebois, Edwin D.; Walusimbi-Nanteza, Maria; Mugerwa, Roy D.; Mayanja, Harriet; Okwera, Alphonse; Whalen, Christopher C.; Havlir, Diane V.
In a prospective randomized, controlled trial in Uganda comparing the efficacy of antiretroviral therapy during tuberculosis therapy with the efficacy of tuberculosis therapy alone in HIV-infected patients with tuberculosis who have a CD4+ cell count >350 cells/µL, it was found that antiretroviral therapy did not accelerate microbiologic, radiographic, or clinical responses to tuberculosis therapy: 18% of participants had sputum smears positive for Mycobacterium tuberculosis after 5 months of tuberculosis therapy, despite having had negative culture results.
Performance of a Score to Characterize Adequate Contact among the Social Network of Persons with Tuberculosis
(Research Square, 2021) Castellanos, Maria Eugenia; Zalwango, Sarah; Quach, Trang; Kakaire, Robert; Martínez, Leonardo; Ebell, Mark H.; Dobbin, Kevin K.; Kiwanuka, Noah; Whalen, Christopher C.
Exposure to an individual with tuberculosis is necessary for transmission to occur. Previously, we developed a score that measures contact between tuberculosis cases and their social networks in an African urban context. This score was built using exploratory factor analysis and identified contact as the conjunction of two domains – setting and relationship. Now, our aim is to determine whether this score covaries with the presence of tuberculous infection among social contacts of tuberculosis cases.
Perinatal HIV Status and Executive Function During School-Age and Adolescence
(Wolters Kluwer Health, 2016) Ezeamama, Amara E.; Kizza, Florence N.; Zalwango, Sarah K.; Nkwata, Allan K.; Zhang, Ming; Rivera, Mariana L.; Sekandi, Juliet N.; Kakaire, Robert; Kiwanuka, Noah; Whalen, Christopher C.
The aim of this study was to determine whether perinatal HIV infection (PHIV), HIV-exposed uninfected (PHEU) versus HIVunexposed (PHU) status predicted long-term executive function (EF) deficit in school-aged Ugandan children. Perinatal HIV status was determined by 18 months via DNA polymerase chain reaction test and confirmed at cognitive assessment between 6 and 18 years using HIV rapid-diagnostic test. Primary outcome is child EF measured using behavior-rating inventory of executive function questionnaire across 8 subscales summed to derive the global executive composite (GEC).
Pertussis Prevalence and Its Determinants among Children with Persistent Cough in Urban Uganda
(PLoS ONE, 2015) Kayina, Vincent; Kyobe, Samuel; Katabazi, Fred A.; Kigozi, Edgar; Okee, Moses; Odongkara, Beatrice; Babikako, Harriet M.; Whalen, Christopher C.; Joloba, Moses L.; Musoke, Philippa M.; Mupere, Ezekiel
We determined prevalence of pertussis infection and its associated host and environmental factors to generate information that would guide strategies for disease control. Methods In a cross-sectional study, 449 children aged 3 months to 12 years with persistent cough lasting 14 days were enrolled and evaluated for pertussis using DNA polymerase chain reaction (PCR) and ELISA serology tests. Results Pertussis prevalence was 67 (15% (95% Confidence Interval (CI): 12–18)) and 81 (20% (95% CI: 16–24)) by PCR and ELISA, respectively among 449 participating children. The prevalence was highest in children with >59 months of age despite high vaccination coverage of 94% in this age group. Study demographic and clinical characteristics were similar between pertussis and non-pertussis cases. Of the 449 children, 133 (30%) had a coughing household member and 316 (70%) did not. Among 133 children that had a coughing household member, sex of child, sharing bed with a coughing household member and having a coughing individual in the neighborhood were factors associated with pertussis. Children that had shared a bed with a coughing household individual had seven-fold likelihood of having pertussis compared to children that did not (odds ratio (OR) 7.16 (95% CI: 1.24– 41.44)). Among the 316 children that did not have a coughing household member, age <23 months, having or contact with a coughing individual in neighborhood, a residence with one room, and having a caretaker with >40 years of age were the factors associated with pertussis. Age <23months was three times more likely to be associated with pertussis compared to age 24–59 months (OR 2.97 (95% CI: 1.07–8.28)). Conclusion Findings suggest high prevalence of pertussis among children with persistent cough at a health facility and it was marked in children >59 months of age, suggesting the possibility of waning immunity. The factors associated with pertussis varied by presence or absence of a coughing household member.
A Radiolabeled Oligonucleotide Ligation Assay Demonstrates the High Frequency of Nevirapine Resistance Mutations in HIV Type 1 Quasispecies of NVP-Treated and Untreated Mother–Infant Pairs from Uganda
(AIDS research and human retroviruses, 2008) Troyer, Ryan M.; Lalonde, Matthew S.; Kyeyune, Fred; Mugyenyi, Peter; Whalen, Christopher C.; Bajunirwe, Francis; Arts, Eric J.
This study explores the levels of NVP and AZT resistance mutations in untreated, NVP- or AZT-treated mother–infant pairs in Uganda. PCR-amplified reverse transcriptase (RT) gene fragments derived from PBMC samples of 85 mothers (10 AZT treated, 35 NVP treated, and 40 untreated) and their 52 infected infants (5 AZT, 9 NVP, and 38 untreated) were classified as subtype A (59%), D (29%), C (3%), and recombinant forms (9%) by population sequencing. Only 16% of the NVP-treated infected mothers and infants harbored either the K103N or the Y181C at 6 weeks postdelivery. The majority of these samples (n = 107) were then analyzed using a radiolabeled oligonucleotide ligation assay (OLA) specific for K70R, K103N, and Y181C, using nonstandard bases to accommodate sequence heterogeneity. By OLA, 43% of the NVP-treated group had K103N and/or Y181C mutations in their HIV-1 population, using >0.6% cutoff based on a comparative clonal analysis of clinical isolates. Surprisingly, an equal fraction of the untreated and NVP-treated mother–infant group had the K103N mutation in their HIV-1 population in the range of 0.6–5%. These findings suggest a relatively high frequency of K103N mutation in the drug-naive, subtype A and D infected Ugandan population as compared to the very low frequency of the Y181C and K70R mutation (<0.6%). The prevalence of the K103N mutations may be related to its low fitness cost and high genetic stability. The persistence of these mutations may reduce the effectiveness of subsequent NVP use in treatment or prevention of perinatal transmission.
Resistance and Susceptibility to Mycobacterium tuberculosis Infection and Disease in Tuberculosis Households in Kampala, Uganda
(Oxford University Press, 2017) Stein, Catherine M.; Zalwango, Sarah; Malone, LaShaunda L.; Thiel, Bonnie; Mupere, Ezekiel; Nsereko, Mary; Okware, Brenda; Kisingo, Hussein; Lancioni, Christina L.; Bark, Charles M.; Whalen, Christopher C.; Joloba, Moses L.; Boom, W. Henry; Mayanja-Kizza, Harriet
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major public health problem. Household contact studies identify children and adults along the spectrum from Mtb exposure to disease. In the Kawempe Community Health Study (conducted in Kampala, Uganda), 872 culture-confirmed pulmonary TB cases and their 2,585 contacts were enrolled during 2002–2012 and followed for up to 2 years each. Risk factors identified by time-to-event analysis for secondary TB differed among children, women, and men. Younger age (P = 0.0061), human immunodeficiency virus (HIV) (P = 0.0002), thinness (P = 0.01), absent bacille Calmette-Guérin vaccination (P = 0.002), and epidemiologic risk score (P < 0.0001) were risks for children. For women, risks were HIV (P < 0.0001), thinness (World Health Organization criteria; P < 0.0001), and epidemiologic risk score (P = 0.003). For men, HIV (P = 0.0007) and low body mass index (P = 0.008) resulted in faster progression to TB. Tuberculin skin testing (TST) identified contacts with Mtb infection and those with persistently negative TST. Risks for faster time to Mtb infection were identified, and included age (P = 0.0007), baseline TST induration (P < 0.0001), and epidemiologic risk score (P < 0.0001) only in children. Those with persistently negative TST comprised 10% of contacts but had no unique epidemiologic characteristics among adults. The burden of Mtb infection and disease is high in TB households, and risk factors for progression from exposure to infection and disease differ among children, women, and men.

Browsing by Author "Whalen, Christopher C."

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