Infectious Diseases Fellow in the Division of Infectious Diseases & Geographic Medicine. Research to benefit under-served populations.
Dr. Seth Ari Sim-Son Hoffman is a clinical postdoctoral fellow in the Stephen P. Luby Lab within the Division of Infectious Diseases & Geographic Medicine, Stanford School of Medicine, Stanford University. His research interests include global health equity and clinical, translational, and implementation research to benefit under-served populations.
Dr. Hoffman is involved in a broad portfolio of impact-driven research to benefit under-served populations including: the PI of typhoid urban water supply surveillance in Liberia; SARS-CoV-2 seroepidemiologic analysis of Gates Foundation-sponsored NORM Trial of a mask promotion/distribution intervention and large-scale study on asymptomatic transmission in Bangladesh; data analysis and publication of a typhoid conjugate vaccine (Typbar-TCV®, Bharat Biotech) rollout in Navi Mumbai, India targeting 9-month to 16-year-old children; a co-investigator on a project attempting to characterize, using shotgun metagenomic sequencing of placentae and environmental heavy metal sampling, why women in Bangladesh suffer from a disproportionately high rate of stillbirth; studying the willingness to receive a Phase II Nipah virus (NiV) vaccine and the appropriate language for communication about a NiV vaccine in Bangladesh.
- Infectious Diseases
- Global Health
- Planetary Health
- Health Equity
- Emerging Infectious Disease
Honors & Awards
Global Health Seed Grant Winner, Stanford Center for Innovation in Global Health (2022)
Benjamin H. Kean Travel Fellowship in Tropical Medicine, American Society of Tropical Medicine & Hygiene (2014)
Boards, Advisory Committees, Professional Organizations
Member, Benjamin Kean Travel Fellowship Award Committee, ASTMH (2023 - Present)
Member, Infectious Diseases Society of America (IDSA) (2020 - Present)
Associate, American College of Physicians (ACP) (2019 - Present)
Member, American Society of Tropical Medicine and Hygiene (ASTMH) (2011 - Present)
MS, Stanford University, Epidemiology and Clinical Research (2023)
Residency, Internal Medicine, University of Maryland Medical Center (2020)
MD, The Medical School for International Health (MSIH), Ben-Gurion University of the Negev Faculty of Health Sciences in affiliation with Columbia University’s Vagelos College of Physicians and Surgeons (2017)
BA, Cornell University, Anthropology (2012)
Retrospective Review of Blood Culture-Confirmed Cases of Enteric Fever in Navi Mumbai, India: 2014-2018.
The American journal of tropical medicine and hygiene
India has one of the highest estimated burdens of enteric fever globally. Prior to the implementation of Typbar-TCV typhoid conjugate vaccine (TCV) in a public sector pediatric immunization campaign in Navi Mumbai, India, we conducted a retrospective review of blood culture-confirmed cases of typhoid and paratyphoid fevers to estimate the local burden of disease. This review included all blood cultures processed at a central microbiology laboratory, serving multiple hospitals, in Navi Mumbai (January 2014-May 2018) that tested positive for either Salmonella Typhi or Salmonella Paratyphi A. Of 40,670 blood cultures analyzed, 1,309 (3.2%) were positive for S. Typhi (1,201 [92%]) or S. Paratyphi A (108 [8%]). Culture positivity was highest in the last months of the dry season (April-June). Our findings indicate a substantial burden of enteric fever in Navi Mumbai and support the importance of TCV immunization campaigns and improved water, sanitation, and hygiene.
View details for DOI 10.4269/ajtmh.23-0102
View details for PubMedID 37549903
Population structure and antimicrobial resistance patterns of Salmonella Typhi and Paratyphi A amid a phased municipal vaccination campaign in Navi Mumbai, India.
We performed whole-genome sequencing of 174 Salmonella Typhi and 54 Salmonella Paratyphi A isolates collected through prospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patterns of emergence and spread of antimicrobial resistance. We evaluated the relationship between the spatial distance between households and genetic clustering of isolates. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing ≥3 quinolone resistance-determining region mutations. Two H58 isolates carried an IncX3 plasmid containing blaSHV-12, associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistant isolates from India independently evolved on multiple occasions. Among S. Typhi, we identified two main clades circulating (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (odds ratio [OR] = 0.72 per km; 95% credible interval [CrI]: 0.66-0.79). This effect was seen for distances up to 5 km (OR = 0.65 per km; 95% CrI: 0.59-0.73) but not seen for distances beyond 5 km (OR = 1.02 per km; 95% CrI: 0.83-1.26). There was a non-significant reduction in odds of clustering for pairs of isolates in vaccination communities compared with non-vaccination communities or mixed pairs compared with non-vaccination communities. Our findings indicate that S. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission. IMPORTANCE Enteric fever remains a major public health concern in many low- and middle-income countries, as antimicrobial resistance (AMR) continues to emerge. Geographical patterns of typhoidal Salmonella spread, critical to monitoring AMR and planning interventions, are poorly understood. We performed whole-genome sequencing of S. Typhi and S. Paratyphi A isolates collected in Navi Mumbai, India before and after a typhoid conjugate vaccine introduction. From timed phylogenies, we found two dominant circulating lineages of S. Typhi in Navi Mumbai-lineage 2.2, which expanded following a single introduction a decade prior, and 4.3.1 (H58), which had been introduced repeatedly from other parts of India, frequently containing "triple mutations" conferring high-level ciprofloxacin resistance. Using Bayesian hierarchical statistical models, we found that spatial distance between cases was strongly associated with genetic clustering at a fine scale (<5 km). Together, these findings suggest that antimicrobial-resistant S. Typhi frequently flows between cities and then spreads highly locally, which may inform surveillance and prevention strategies.
View details for DOI 10.1128/mbio.01179-23
View details for PubMedID 37504577
Programmatic Effectiveness of a Pediatric Typhoid Conjugate Vaccine Campaign in Navi Mumbai, India.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
The WHO recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018 the Navi Mumbai Municipal Corporation (NMMC), implemented a TCV campaign. The campaign targeted all children aged 9-months through 14-years within NMMC boundaries (∼320,000 children) over 2 vaccination phases. The phase 1 campaign occurred from July 14-August 25, 2018 (71% coverage, ∼113,420 children). We evaluated the phase 1 campaign's programmatic effectiveness in reducing typhoid cases at the community level.We established prospective, blood culture-based surveillance at 6 hospitals in Navi Mumbai, offering blood cultures to children presenting with fever ≥ 3 days. We employed a cluster-randomized (by administrative boundary) test-negative design to estimate the effectiveness of the vaccination campaign on pediatric typhoid cases. We matched test-positive, culture-confirmed typhoid cases with up to 3 test-negative, culture-negative controls by age and date of blood culture and assessed community vaccine campaign phase as an exposure using conditional logistic regression.Between September 1, 2018-March 31, 2021, we identified 81 typhoid cases and matched these with 238 controls. Cases were 0.44 times as likely to live in vaccine campaign communities (programmatic effectiveness, 56%, 95%CI: 25%-74%, p=0.002). Cases ≥ 5-years-old were 0.37 times as likely (95% CI: 0.19-0.70; p-value = 0.002) and cases during the first year of surveillance were 0.30 times as likely (95% CI: 0.14-0.64; p-value = 0.002) to live in vaccine campaign communities.Our findings support the use of TCV mass vaccination campaigns as effective population-based tools to combat typhoid fever.
View details for DOI 10.1093/cid/ciad132
View details for PubMedID 36947143
Chronic Salmonella Typhi carriage at sites other than the gallbladder.
PLoS neglected tropical diseases
2023; 17 (3): e0011168
Typhoid fever caused by infection with Salmonella enterica subspecies enterica serotype Typhi (S. Typhi), an important public health problem in many low- and middle-income countries, is transmitted by ingestion of water or food contaminated by feces or urine from individuals with acute or chronic S. Typhi infection. Most chronic S. Typhi carriers (shedding for ≥12 months) harbor infection in their gallbladder wherein preexisting pathologies, particularly cholelithiasis, provide an environment that fosters persistence. Much less appreciated is the existence of non-gallbladder hepatobiliary chronic S. Typhi carriers and urinary carriers. The former includes parasitic liver flukes as a chronic carriage risk factor. Chronic urinary carriers typically have pathology of their urinary tract, with or without renal or bladder stones. Even as the prevalence of multidrug-resistant and extensively drug-resistant S. Typhi strains is rising, global implementation of highly effective typhoid vaccines is increasing. There is also renewed interest in identifying, monitoring, and (where possible) treating chronic carriers who comprise the long-term reservoir of S. Typhi.
View details for DOI 10.1371/journal.pntd.0011168
View details for PubMedID 36952437
View details for PubMedCentralID PMC10035749
Point-of-Care Ultrasound by Nonexpert Operators Demonstrates High Sensitivity and Specificity in Detecting Gallstones: Data from the Samoa Typhoid Fever Control Program.
The American journal of tropical medicine and hygiene
Approximately 90% of chronic typhoid carriers with persistent Salmonella enterica serovar Typhi (S. Typhi) gallbladder infection have gallstones. In Samoa, where typhoid fever has been endemic for many decades, risk factors predisposing to the development of gallstones are increasing among adults. The Samoa Typhoid Fever Control Program dispatches a "Typhoid Epidemiologic SWAT Team" to perform a household investigation of every blood culture-confirmed case of acute typhoid fever. Investigations include screening household contacts to detect chronic carriers. Following limited training, two nonexpert ultrasound operators performed point-of-care ultrasound (POCUS) on 120 Samoan adults from August to September 2019 to explore the feasibility of POCUS to detect individuals with gallstones during household investigations and community screenings. POCUS scans from 120 Samoan adults in three cohorts (28 food handlers, two typhoid cases and their 18 household contacts, and 72 attendees at an ambulatory clinic) were reviewed by a board-certified radiologist who deemed 96/120 scans (80%) to be interpretable. Compared with the radiologist (gold standard), the nonexpert operators successfully detected 6/7 Samoans with gallstones (85.7% sensitivity) and correctly identified 85/89 without gallstones (95.5% specificity). The proportion (24/120) of uninterpretable scans from this pilot that used minimally trained clinicians (who are neither radiologists nor ultrasound technicians) indicates the need for additional training of POCUS operators. Nevertheless, this pilot feasibility study engenders optimism that in the Samoan setting nonexperts can be trained to use POCUS to diagnose cholelithiasis, thereby helping (along with stool cultures and Vi serology) to identify possible chronic S. Typhi carriers.
View details for DOI 10.4269/ajtmh.21-0973
View details for PubMedID 35008059
SARS-CoV-2 Neutralization Resistance Mutations in Patient with HIV/AIDS, California, USA.
Emerging infectious diseases
2021; 27 (10)
We report persistent severe acute respiratory syndrome coronavirus 2 infection in a patient with HIV/AIDS; the virus developed spike N terminal domain and receptor binding domain neutralization resistance mutations. Our findings suggest that immunocompromised patients can harbor emerging variants of severe acute respiratory syndrome coronavirus 2.
View details for DOI 10.3201/eid2710.211461
View details for PubMedID 34296992
Tenacious Endemic Typhoid Fever in Samoa.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
2020; 71 (Supplement_2): S120-S126
Typhoid fever has been endemic on the island nation of Samoa (2016 population, 195 979) since the 1960s and has persisted through 2019, despite economic development and improvements in water supply and sanitation.Salmonella enterica serovar Typhi isolates from the 2 hospitals with blood culture capability and matched patient demographic and clinical data from January 2008 through December 2019 were analyzed. Denominators to calculate incidence by island, region, and district came from 2011 and 2016 censuses and from 2017-2019 projections from Samoa's Bureau of Statistics. Data were analyzed to describe typhoid case burden and incidence from 2008 to 2019 by time, place, and person.In sum, 53-193 blood culture-confirmed typhoid cases occurred annually from 2008 to 2019, without apparent seasonality. Typhoid incidence was low among children age < 48 months (17.6-27.8/105), rose progressively in ages 5-9 years (54.0/105), 10-19 years (60.7-63.4/105), and 20-34 years (61.0-79.3/105), and then tapered off; 93.6% of cases occurred among Samoans < 50 years of age. Most typhoid cases and the highest incidence occurred in Northwest Upolu, but Apia Urban Area (served by treated water supplies) also exhibited moderate incidence. The proportion of cases from short-cycle versus long-cycle transmission is unknown. Samoan S. Typhi are pansusceptible to traditional first-line antibiotics. Nevertheless, enhanced surveillance in 2019 detected 4 (2.9%) deaths among 140 cases.Typhoid has been endemic in Samoa in the period 2008-2019. Interventions, including mass vaccination with a Vi-conjugate vaccine coadministered with measles vaccine are planned.
View details for DOI 10.1093/cid/ciaa314
View details for PubMedID 32725232
Miliary pattern on chest imaging as a presentation of EGFR-negative primary lung adenocarcinoma.
BMJ case reports
2019; 12 (5)
A 64-year-old African American man, with a history of prostate adenocarcinoma treated in 2009 and a greater than 50-pack-year tobacco smoking history, presented with 2-3 weeks of non-productive cough, frontal headache and generalised myalgias and arthralgias. CT was positive for diffuse, miliary opacities in bilateral lung fields. He was diagnosed with stage four lung adenocarcinoma, negative for epidermal growth factor receptor (EGFR) gene mutation. The patient was unable to tolerate therapy and passed away approximately 4 months after his diagnosis. Previous case reports and research have suggested an association between EGFR gene mutation and miliary patterned lung metastases in non-small cell lung cancer. This case suggests that the mechanism by which miliary patterned metastases occur is more complex than purely mutation of the EGFR gene. Further study may elucidate novel molecular targets for treatment, especially in patients with rapidly progressive disease such as the patient we describe.
View details for DOI 10.1136/bcr-2018-228534
View details for PubMedID 31151972
Female Anopheles gambiae antennae: increased transcript accumulation of the mosquito-specific odorant-binding-protein OBP2.
Parasites & vectors
2012; 5: 27
New interventions are required to optimally and sustainably control the Anopheles sp. mosquitoes that transmit malaria and filariasis. The mosquito olfactory system is important in host seeking (transmission) and mate finding (reproduction). Understanding olfactory function could lead to development of control strategies based on repelling parasite-carrying mosquitoes or attracting them into a fatal trap.Our initial focus is on odorant binding proteins with differential transcript accumulation between female and male mosquitoes. We report that the odorant binding protein, OBP2 (AGAP003306), had increased expression in the antennae of female vs. male Anopheles gambiae sensu stricto (G3 strain). The increased expression in antennae of females of this gene by quantitative RT-PCR was 4.2 to 32.3 fold in three independent biological replicates and two technical replicate experiments using A. gambiae from two different laboratories. OBP2 is a member of the vast OBP superfamily of insect odorant binding proteins and belongs to the predominantly dipteran clade that includes the Culex oviposition kairomone-binding OBP1. Phylogenetic analysis indicates that its orthologs are present across culicid mosquitoes and are likely to play a conserved role in recognizing a molecule that might be critical for female behavior.OBP2 has increased mRNA transcript accumulation in the antennae of female as compared to male A. gambiae. This molecule and related molecules may play an important role in female mosquito feeding and breeding behavior. This finding may be a step toward providing a foundation for understanding mosquito olfactory requirements and developing control strategies based on reducing mosquito feeding and breeding success.
View details for DOI 10.1186/1756-3305-5-27
View details for PubMedID 22309624
View details for PubMedCentralID PMC3297500
Programmed Cell Death during Malaria Parasite Infection of the Vertebrate Host and Mosquito Vector
Programmed Cell Death in Protozoa
edited by Perez Martin, J.
Springer. 2008: 74–90
View details for DOI 10.1007/978-0-387-76717-8_7
Light deprivation affects larval development and arrestin gene expression in Anopheles stephensi.
Journal of medical entomology
2005; 42 (5): 801-4
The role of light exposure on the final stages of development of Anopheles stephensi larvae to pupae and adult mosquitoes was explored. We demonstrated a significant reduction in the development of adult mosquitoes when larvae were bred in the absence of light compared with the control group bred in alternating 12 h of light and 12 h of dark. To correlate these findings at the molecular level, RNA levels of the visual arrestin gene were examined. Arrestins are an important gene family that play a role in the vectorial capacity of Anopheles and mediate neurotransmission as well as olfactory and visual sensory reception in insects. Semiquantitative polymerase chain reaction showed a reduction in the expression of the visual arrestin gene in pupae that developed from larvae in the absence of light compared with larvae bred under normal conditions.
View details for DOI 10.1093/jmedent/42.5.801
View details for PubMedID 16363162