Aslam Khan

All Publications

• Spatiotemporal overlapping of dengue, chikungunya, and malaria infections in children in Kenya. BMC infectious diseases Khan, A., Bisanzio, D., Mutuku, F., Ndenga, B., Grossi-Soyster, E. N., Jembe, Z., Maina, P. W., Chebii, P. K., Ronga, C. O., Okuta, V., LaBeaud, A. D. 2023; 23 (1): 183

  Abstract

  Malaria, chikungunya virus (CHIKV), and dengue virus (DENV) are endemic causes of fever among children in Kenya. The risks of infection are multifactorial and may be influenced by built and social environments. The high resolution overlapping of these diseases and factors affecting their spatial heterogeneity has not been investigated in Kenya. From 2014-2018, we prospectively followed a cohort of children from four communities in both coastal and western Kenya. Overall, 9.8% were CHIKV seropositive, 5.5% were DENV seropositive, and 39.1% were malaria positive (3521 children tested). The spatial analysis identified hot-spots for all three diseases in each site and in multiple years. The results of the model showed that the risk of exposure was linked to demographics with common factors for the three diseases including the presence of litter, crowded households, and higher wealth in these communities. These insights are of high importance to improve surveillance and targeted control of mosquito-borne diseases in Kenya.

  View details for DOI 10.1186/s12879-023-08157-4

  View details for PubMedID 36991340

  View details for PubMedCentralID 6881070

• Respiratory Failure in an 11-day-old Neonate. NeoReviews Aiden, A. P., Khan, A., Schwenk, H., Fuerch, J. H. 2023; 24 (1): 36-38

  View details for DOI 10.1542/neo.24-1-e36

  View details for PubMedID 36587004

• Yellow Fever Molecular Diagnosis Using Urine Specimens during Acute and Convalescent Phases of the Disease. Journal of clinical microbiology de Rezende, I. M., Oliveira, G. F., Costa, T. A., Khan, A., Pereira, L. S., Santos, T. A., Alves, P. A., Calzavara-Silva, C. E., Martins-Filho, O. A., Teixeira-Carvalho, A., LaBeaud, A. D., Drumond, B. P. 2022: e0025422

  Abstract

  Prior studies have demonstrated prolonged presence of yellow fever virus (YFV) RNA in saliva and urine as an alternative to serum. To investigate the presence of YFV RNA in urine, we used RT-PCR for YFV screening in 60 urine samples collected from a large cohort of naturally infected yellow fever (YF) patients during acute and convalescent phases of YF infection from recent YF outbreaks in Brazil (2017 to 2018). Fifteen urine samples from acute phase infection (up to 15days post-symptom onset) and four urine samples from convalescent phase infection (up to 69days post-symptom onset), were YFV PCR-positive. We genotyped YFV detected in seven urine samples (five collected during the acute phase and two collected during the YF convalescent phase). Genotyping indicated the presence of YFV South American I genotype in these samples. To our knowledge, this is the first report of wild-type YFV RNA detection in the urine this far out from symptom onset (up to 69 DPS), including YFV RNA detection during the convalescent phase of YF infection. The detection of YFV RNA in urine is an indicative of YFV infection; however, the results of RT-PCR using urine as sample should be interpreted with care, since a negative result does not exclude the possibility of YFV infection. With a possible prolonged period of detection beyond the viremic phase, the use of urine samples coupled with serological tests, epidemiologic inquiry, and clinical assessment could provide a longer diagnostic window for laboratory YF diagnosis.

  View details for DOI 10.1128/jcm.00254-22

  View details for PubMedID 35916519

• Near-fatal Legionella pneumonia in a neonate linked to home humidifier by metagenomic next generation sequencing. Med (New York, N.Y.) West, P. T., Brooks, E. F., Costales, C., Moreno, A., Jensen, T. D., Budvytiene, I., Khan, A., Pham, T. H., Schwenk, H. T., Bhatt, A. S., Banaei, N. 2022

  View details for DOI 10.1016/j.medj.2022.06.004

  View details for PubMedID 35863347

• Characterizing the Severity of SARS-CoV-2 Variants at a Single Pediatric Center FRONTIERS IN MEDICINE Khan, A., Ichura, C., Wang, H., Rezende, I., Sahoo, M. K., Huang, C., Solis, D., Sibai, M., Yamamoto, F., Nyathi, S., Bayrau, B., Pinsky, B. A., LaBeaud, A. 2022; 9: 896352

  Abstract

  Since March 2020, SARS-CoV-2 has plagued the world with COVID-19 and individuals of all ages have experienced varying symptoms of disease. Older adults were experiencing more severe disease compared to children and were prioritized by vaccination efforts. While biologic therapies and vaccinations were implemented, there were changes in public health restrictions with subsequent surges resulting in more infected children. During these surges there was a rise of different SARS-CoV-2 variants with the dominant variant initially alpha (B.1.1.7 and other Pango lineages) and epsilon (B.1.427/B.1.429) in early 2021 and a dramatic shift to delta (B.1.617.2 and other Pango lineages) by mid-summer 2021. In this study we aimed to characterize the clinical severity and host factors associated with disease by SARS-CoV-2 variant and evaluate if there are differences in disease severity by circulating variant. We retrospectively included all individuals 0-25 years of age who presented to our center and had a positive SARS-CoV-2 RT-PCR, SARS-CoV-2 variant mutation testing, and documented clinical notes from 1 January 2021 through 31 December 2021. We identified 745 individuals who met inclusion criteria and found the delta variant was associated with severe/critical disease compared to the other variants studied. The results of the model showed that underlying respiratory disease and diabetes were risk factors for progression to severe disease. These insights are important when evaluating public health measures and treatment options for children as more variants arise.

  View details for DOI 10.3389/fmed.2022.896352

  View details for Web of Science ID 000807127000001

  View details for PubMedID 35677819

  View details for PubMedCentralID PMC9168367

• Majority of pediatric dengue virus infections in Kenya do not meet 2009 WHO criteria for dengue diagnosis. PLOS global public health Khan, A., Ndenga, B., Mutuku, F., Bosire, C. M., Okuta, V., Ronga, C. O., Mutai, N. K., Musaki, S. K., Chebii, P. K., Maina, P. W., Jembe, Z., Amugongo, J. S., Malumbo, S. L., Ng'ang'a, C. M., LaBeaud, D. 2022; 2 (4): e0000175

  Abstract

  From 1975-2009, the WHO guidelines classified symptomatic dengue virus infections as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. In 2009 the case definition was changed to a clinical classification after concern the original criteria was challenging to apply in resource-limited settings and not inclusive of a substantial proportion of severe dengue cases. Our goal was to examine how well the current WHO definition identified new dengue cases at our febrile surveillance sites in Kenya. Between 2014 and 2019 as part of a child cohort study of febrile illness in our four clinical study sites (Ukunda, Kisumu, Msambweni, Chulaimbo) we identified 369 dengue PCR positive symptomatic cases and characterized whether they met the 2009 revised WHO diagnostic criteria for dengue with and without warning signs and severe dengue. We found 62% of our PCR-confirmed dengue cases did not meet criteria per the guidelines. Our findings also correlate with our experience that dengue disease in children in Kenya is less severe as reported in other parts of the world. Although the 2009 clinical classification has recently been criticized for being overly inclusive and non-specific, our findings suggest the 2009 WHO dengue case definition may miss more than 50% of symptomatic infections in Kenya and may require further modification to include the African experience.

  View details for DOI 10.1371/journal.pgph.0000175

  View details for PubMedID 36962138

• URINE AS A POSSIBLE RESOURCE FOR YELLOW FEVER DIAGNOSIS Rezende, I. M., Pereira, L. S., Khan, A., Oliveira, G. G., Alkifeles, T., Goncalves, A. P., Alves, P. A., Martins-Filho, O. A., Teixeira-Carvalho, A., LaBeaud, A., Drumond, B. P. AMER SOC TROP MED & HYGIENE. 2021: 187

  View details for Web of Science ID 000778105602276

• SPATIOTEMPORAL OVERLAPPING OF DENGUE, CHIKUNGUNYA, AND MALARIA INFECTIONS IN CHILDREN IN KENYA Khan, A., Bisanzio, D., Mutuku, F., Ndenga, B., Jembe, Z., Maina, P., Chebii, P., Ronga, C., Mwambingu, L., Okuta, V., LaBeaud, D. AMER SOC TROP MED & HYGIENE. 2021: 44-45

  View details for Web of Science ID 000778105601139

• USING MHEALTH SMS SURVEYS FOR ACTIVE SURVEILLANCE OF FEBRILE ILLNESS IN KENYA Ivory, J., Khan, A., Mutuku, F., Ndenga, B., Ronga, C., Godana, O., Mwangosho, K., Wanjala, L., Okuta, V., Jembe, Z., Agola, G., Kang, A., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2021: 31

  View details for Web of Science ID 000778105601094

• MAJORITY OF PEDIATRIC DENGUE VIRUS INFECTIONS IN KENYA DO NOT MEET THE 2009 WHO CRITERIA FOR DENGUE DIAGNOSIS Khan, A., Ndenga, B., Mutuku, F., Ronga, C., Mwambingu, L., Okuta, V., Jembe, Z., Maina, P., Chebii, P., LaBeaud, D. AMER SOC TROP MED & HYGIENE. 2021: 185

  View details for Web of Science ID 000778105602270

• Toxoplasmosis in Pediatric Hematopoietic Stem Cell Transplantation Patients. Transplantation and cellular therapy Schwenk, H. T., Khan, A., Kohlman, K., Bertaina, A., Cho, S., Montoya, J. G., Contopoulos-Ioannidis, D. G. 2021; 27 (4): 292–300

  Abstract

  Infection due to the protozoa Toxoplasma gondii can be life-threatening in hematopoietic stem cell transplantation (HSCT) recipients. Most cases of toxoplasmosis in HSCT recipients result from reactivation of latent infection in individuals who were Toxoplasma-seropositive before transplantation and did not receive appropriate prophylaxis. Pretransplantation screening with Toxoplasma IgG and IgM antibodies is suggested for all allogeneic HSCT recipients and their donors and all autologous HSCT recipients. Prevention of toxoplasmosis in T. gondii-seropositive HSCT recipients requires primary prophylaxis, preemptive screening, or both. Trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred agent for Toxoplasma prophylaxis and should be continued for 6 months or until the patient is no longer receiving immunosuppression, whichever is longer, assuming that immune reconstitution has occurred. Preemptive weekly screening with whole blood Toxoplasma PCR should be considered for seropositive HSCT recipients if prophylaxis cannot be given or if prophylaxis other than TMP-SMX is used. The signs, symptoms, and radiographic findings of toxoplasmosis in HSCT recipients can be nonspecific, and the diagnosis requires a high degree of suspicion. Common presentations include fever, encephalopathy with mental status changes or seizures, and pneumonia. A Toxoplasma PCR analysis from whole blood (and other body fluids/tissues according to clinical symptoms) should be obtained in patients in whom there is a concern for toxoplasmosis. Treatment with oral pyrimethamine, sulfadiazine, and leucovorin for at least 6 weeks is the first-line therapy and should be followed by secondary prophylaxis. In this article, we review the published literature regarding the epidemiology, clinical presentation, treatment, and prevention of toxoplasmosis in HSCT recipients.

  View details for DOI 10.1016/j.jtct.2020.11.003

  View details for PubMedID 33840441

• Response to Trimethoprim-Sulfamethoxazole in a Pediatric Hematopoietic Stem Cell Transplant Recipient With Disseminated Toxoplasmosis: A Case Report. Journal of the Pediatric Infectious Diseases Society Khan, A., Schwenk, H. T., Kohlman, K., Bertaina, A., Cho, S., Montoya, J. G., Contopoulos-Ioannidis, D. 2021

  Abstract

  We describe the presentation and treatment of a patient who developed ongoing fever and diagnosed with disseminated toxoplasmosis post-hematopoietic stem cell transplantation. He was initially treated with trimethoprim-sulfamethoxazole (TMP-SMX) and there was dramatic improvement in his fever curve. He successfully completed a modified course of therapy.

  View details for DOI 10.1093/jpids/piab006

  View details for PubMedID 33693793

• Young Boy With Fatigue and Weight Loss. Annals of emergency medicine Khan, A., Ho, C. H., Chan, R. Y. 2018; 71 (4): e53-e54

  View details for DOI 10.1016/j.annemergmed.2017.11.009

  View details for PubMedID 29566901

• Extracellular superoxide dismutase is important for hippocampal neurogenesis and preservation of cognitive functions after irradiation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Zou, Y., Corniola, R., Leu, D., Khan, A., Sahbaie, P., Chakraborti, A., Clark, D. J., Fike, J. R., Huang, T. 2012; 109 (52): 21522-21527

  Abstract

  Cranial irradiation is widely used in cancer therapy, but it often causes cognitive defects in cancer survivors. Oxidative stress is considered a major cause of tissue injury from irradiation. However, in an earlier study mice deficient in the antioxidant enzyme extracellular superoxide dismutase (EC-SOD KO) showed reduced sensitivity to radiation-induced defects in hippocampal functions. To further dissect the role of EC-SOD in neurogenesis and in response to irradiation, we generated a bigenic EC-SOD mouse model (OE mice) that expressed high levels of EC-SOD in mature neurons in an otherwise EC-SOD-deficient environment. EC-SOD deficiency was associated with reduced progenitor cell proliferation in the subgranular zone of dentate gyrus in KO and OE mice. However, high levels of EC-SOD in the granule cell layer supported normal maturation of newborn neurons in OE mice. Following irradiation, wild-type mice showed reduced hippocampal neurogenesis, reduced dendritic spine densities, and defects in cognitive functions. OE and KO mice, on the other hand, were largely unaffected, and the mice performed normally in neurocognitive tests. Although the resulting hippocampal-related functions were similar in OE and KO mice following cranial irradiation, molecular analyses suggested that they may be governed by different mechanisms: whereas neurotrophic factors may influence radiation responses in OE mice, dendritic maintenance may be important in the KO environment. Taken together, our data suggest that EC-SOD plays an important role in all stages of hippocampal neurogenesis and its associated cognitive functions, and that high-level EC-SOD may provide protection against irradiation-related defects in hippocampal functions.

  View details for DOI 10.1073/pnas.1216913110

  View details for Web of Science ID 000313627700077

  View details for PubMedID 23236175

  View details for PubMedCentralID PMC3535634

• Characterization of Humoral Immune Responses to Chlamydial HSP60, CPAF, and CT795 in Inflammatory and Severe Trachoma INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Skwor, T., Kandel, R., Basravi, S., Khan, A., Sharma, B., Dean, D. 2010; 51 (10): 5128-5136

  Abstract

  Chlamydia trachomatis (Ct) remains the leading global cause of preventable blindness. There are limited data on humoral immune responses in trachoma. Evaluating these responses is important for understanding host-pathogen interactions and informing vaccine design. Antibodies to chlamydial heat shock protein 60 (cHSP60) have been associated with infertility and trachomatous scarring. Other proteins, including chlamydial protease-associated factor (CPAF) and a hypothetical protein unique to the family Chlamydiaceae, CT795, elicit strong immune responses in urogenital infections, but their role in trachomatous disease is unknown.This study was conducted to expand on previous cHSP60 findings and evaluate the association of CPAF and CT795 antibodies with ocular Ct infection and disease. Clinical trachoma grading was performed, and conjunctival samples were obtained from individuals with trachomatous trichiasis (TT; one or more inturned eyelashes) or inflammatory trachoma without trichiasis and control subjects without disease, all of whom resided in trachoma-endemic regions of Nepal. Ct infection was determined using commercial PCR. IgG and IgA tear antibodies against cHSP60, CT795, and CPAF fusion proteins were measured by quantitative ELISA.Significantly higher IgG antibody levels were found against cHSP60, CPAF, and CT795 in the inflammatory cases compared with levels in the controls (P < 0.005 for all three). Ct infection was independently associated with IgG antibodies against all three immunogens in the inflammatory cases but not in the controls (P = 0.025, P = 0.03 and P = 0.017, respectively). Only IgG antibodies against CPAF were significantly elevated among the TT cases (P = 0.013).Among individuals with trachoma, IgG antibody responses to CPAF are likely to be both a marker and risk factor for inflammatory trachoma and severe trachomatous disease.

  View details for DOI 10.1167/iovs.09-5113

  View details for Web of Science ID 000282275500035

  View details for PubMedID 20463311

  View details for PubMedCentralID PMC3066612

• Enhanced expression of mitochondrial superoxide dismutase leads to prolonged in vivo cell cycle progression and up-regulation of mitochondrial thioredoxin FREE RADICAL BIOLOGY AND MEDICINE Kim, A., Joseph, S., Khan, A., Epstein, C. J., Sobel, R., Huang, T. 2010; 48 (11): 1501-1512

  Abstract

  Mn superoxide dismutase (MnSOD) is an important mitochondrial antioxidant enzyme, and elevated MnSOD levels have been shown to reduce tumor growth in part by suppressing cell proliferation. Studies with fibroblasts have shown that increased MnSOD expression prolongs cell cycle transition time in G1/S and favors entrance into the quiescent state. To determine if the same effect occurs during tissue regeneration in vivo, we used a transgenic mouse system with liver-specific MnSOD expression and a partial hepatectomy paradigm to induce synchronized in vivo cell proliferation during liver regeneration. We show in this experimental system that a 2.6-fold increase in MnSOD activity leads to delayed entry into S phase, as measured by reduction in bromodeoxyuridine (BrdU) incorporation and decreased expression of proliferative cell nuclear antigen (PCNA). Thus, compared to control mice with baseline MnSOD levels, transgenic mice with increased MnSOD expression in the liver have 23% fewer BrdU-positive cells and a marked attenuation of PCNA expression. The increase in MnSOD activity also leads to an increase in the mitochondrial form of thioredoxin (thioredoxin 2), but not in several other peroxidases examined, suggesting the importance of thioredoxin 2 in maintaining redox balance in mitochondria with elevated levels of MnSOD.

  View details for DOI 10.1016/j.freeradbiomed.2010.02.028

  View details for PubMedID 20188820

• EC-SOD Deficiency Affects in Vitro Propagation and Differentiation of Neuronal Progenitor Cells 16th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine Zou, Y., Khan, A., Dragoescu, M., Huang, T. ELSEVIER SCIENCE INC. 2009: S116–S116

  View details for Web of Science ID 000271988500327