Papers by Stephen Waterman
Dengue epidemiology and vaccine development
PLOS global public health, Jul 7, 2023
Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; the... more Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here:

PLOS Computational Biology, Mar 30, 2021
Emerging epidemics are challenging to track. Only a subset of cases is recognized and reported, a... more Emerging epidemics are challenging to track. Only a subset of cases is recognized and reported, as seen with the Zika virus (ZIKV) epidemic where large proportions of infection were asymptomatic. However, multiple imperfect indicators of infection provide an opportunity to estimate the underlying incidence of infection. We developed a modeling approach that integrates a generic Time-series Susceptible-Infected-Recovered epidemic model with assumptions about reporting biases in a Bayesian framework and applied it to the 2016 Zika epidemic in Puerto Rico using three indicators: suspected arboviral cases, suspected Zikaassociated Guillain-Barré Syndrome cases, and blood bank data. Using this combination of surveillance data, we estimated the peak of the epidemic occurred during the week of August 15, 2016 (the 33 rd week of year), and 120 to 140 (50% credible interval [CrI], 95% CrI: 97 to 170) weekly infections per 10,000 population occurred at the peak. By the end of 2016, we estimated that approximately 890,000 (95% CrI: 660,000 to 1,100,000) individuals were infected in 2016 (26%, 95% CrI: 19% to 33%, of the population infected). Utilizing multiple indicators offers the opportunity for real-time and retrospective situational awareness to support epidemic preparedness and response.
Meningococcal Disease in the United States--1986
The Journal of Infectious Diseases, Aug 1, 1991
Active surveillance for invasive meningococcal disease was conducted during 1986 and 1987 in six ... more Active surveillance for invasive meningococcal disease was conducted during 1986 and 1987 in six areas of the United States with a total population of ?34 million persons. The incidence of meningococcal disease was 1.3:105 . The highest incidence of disease among the ...
Annals of Epidemiology, Sep 1, 2008
Methicillin-resistant Staphylococcus aureus skin infections from an elephant calf - San Diego, California, 2008
Morbidity and Mortality Weekly Report, 2009

Open Forum Infectious Diseases, 2017
Background. While Zika virus (ZIKV) infection is typically self-limited, congenital birth defects... more Background. While Zika virus (ZIKV) infection is typically self-limited, congenital birth defects and Guillain-Barré syndrome are well-described. There are no therapies or vaccines against ZIKV infection. Methods. ZIKA-001 is a phase I, open label, clinical trial designed to evaluate the safety, side effect profile, and immunogenicity of a synthetic, DNA vaccine (GLS-5700) targeting the pre-membrane+envelope proteins (prME) of the virus. Two groups of 20 participants received GLS-5700 at one of two dose levels: 1 mg or 2 mg DNA/dose at 0, 4, and 12 weeks. Vaccine was administered as 0.1 or 0.2 ml (1 or 2 mg) intradermal (ID) injection followed by electroporation (EP) with the CELLECTRA ®-3P device Results. The median age of the 40 participants was 38 (IQR 30-54) years; 60% were female 30% Latino and 78% white. No SAEs have been reported to date. Local minor AEs were injection site pain, redness, swelling and itching that occurred in half of the participants. Systemic adverse events were rare and included headache, myalgias, upper respiratory infections, fatigue/malaise and nausea. Four weeks after the first dose 25% vs. 60% of the participants in the 1 mg and 2 mg dose seroconverted. By week 6, 2 weeks after the second dose, the response was 65 and 84% respectively and 2 weeks after the third dose all participants in both dosing groups developed antibodies. At the end of the vaccination period over 60% of vaccinated person neutralized Zika virus in a vero cell assay and greater than 80% on neuronal cell targets. The protective efficacy of the antibodies generated by the vaccine was evaluated in the lethal IFNAR−/− mouse model. After the intraperitoneal administration of 0.1 ml of either baseline, week 14 serum or PBS the animals were challenged with 10 6 PFUs of ZIKV PR209 isolate. Whereas animals administered PBS (control) or baseline serum succumbed after a median of 5 days, those pretreated with week 14 serum from study participants survived suggesting that the humoral response generated by the vaccine is protective in this model. Conclusion. Our trial shows for the first time in humans the safety and immunogenicity of an engineered DNA encoding consensus viral protein against ZIKV. Future studies will evaluate the effectiveness of the vaccine.

Public health reports (Washington, D.C. : 1974)
A study was undertaken to determine the extent of measles underreporting among preschool-age chil... more A study was undertaken to determine the extent of measles underreporting among preschool-age children. In two community surveys conducted in inner-city Los Angeles during 1990 and 1991, respondents were asked whether preschool-age children in their households had ever been ill with measles. Information about measles episodes was obtained and medical records were reviewed, when available. A probable measles case was defined as having 3 or more days of rash with fever of 38.3 degrees centigrade or greater, and either cough, coryza, or conjunctivitis. To determine the proportion of cases reported, probable measles cases identified were matched with measles cases reported to the Los Angeles County Department of Health Services. Of the 947 children ages 6 weeks through 59 months included in the surveys, 35 children had experienced an illness episode which met the probable measles case definition. Ten (29 percent) of the 35 probable measles cases were reported to the health department. Ho...

International Journal of Dermatology, 1985
Patients with confirmed dengue infection were studied in .in attempt to elucidate the cause of th... more Patients with confirmed dengue infection were studied in .in attempt to elucidate the cause of the eruption of denguv fever. Punch biopsies 01 leuonal skin were obUvned iind processed for thv presence of viral dnti^en diul immunv globulins by the direct fluorescent antibody test. Another biopsy specimen and the acute sera were processed for virus isolation. Although virus was isolated from the serum of fwo patients, isolation attempts from the biopsy specimen^ 01 all four patients were riegative. fluorescent antibody studies revested no evidence ot either viral antigen or immune globulins in lesional skin. Although limited, the data suggest tlwt the m.Hiilopapular rash oi dvnfiut* fever may be caused by some mechanism other than direct viral infection of the skin or involvement of immune Dengue fever is a mosquilo-borne viral illness that classically is characteri/eti by sudden onset ot lever, chills, frontal headache, myalgias, anorexia, and nausea and vomiting.'"' The acute illness generally lasts 3-7 days, but convalescence may be prolonged antI accompanied by weakness and depression. An erythematous, macular, or maculopapular rash often appears .ifler ^-h days of illness. It is generally nol possible to differentiate between the four dengue serotypes on the basis of clinical syndromes. Dengue 4 was introduced into Puerto Rico in September 1981, at the height of a dengue I epidemic.
Dengue fever
Clinics in Dermatology, 1989
A Case of Natural Concurrent Human Infection with Two Dengue Viruses
American Journal of Tropical Medicine and Hygiene, 1985
The first documented case of concurrent human infection with 2 dengue viruses is reported. Dengue... more The first documented case of concurrent human infection with 2 dengue viruses is reported. Dengue 1 and 4 viruses were isolated from the serum of a 16-year-old male during the 1982 outbreak in Puerto Rico. The illness was mild and does not support the hypothesis that double infection with dengue viruses leads to more severe hemorrhagic disease.

Travel Medicine and Infectious Disease, 2019
Background: The high volume of US-Mexico land border crossings can facilitate international disse... more Background: The high volume of US-Mexico land border crossings can facilitate international dissemination of influenza viruses. Methods: We surveyed adult pedestrians crossing into the United States at two international land ports of entry to assess vaccination coverage during the 2009H1N1 influenza pandemic and 2011-2012 influenza season. Results: Of 559 participants in 2010, 23.4% reported receipt of the 2009H1N1 vaccine. Of 1423 participants in 2012, 33.7% received the 2011-2012 influenza vaccine. Both years, those crossing the border ≥8 times per month had lower vaccination coverage than those crossing less frequently. US-border residents had lower H1N1 coverage than those in other locations. Vaccination coverage was higher for persons age ≥65 years and, in 2010 only, those with less than high school education. Although most participants believed it is important to get vaccinated, only half believed the influenza vaccine was safe and effective. The main reasons for not receiving the influenza vaccine were beliefs of low risk of disease, time constraints, and concerns about vaccine safety (in 2010) or efficacy (in 2012).

American Journal of Tropical Medicine and Hygiene, Jan 30, 2017
Dengue, a mosquito-borne viral disease, is increasingly being identified as a cause of outbreaks ... more Dengue, a mosquito-borne viral disease, is increasingly being identified as a cause of outbreaks in the United States. During July-December 2013, a total of three south Texas counties reported 53 laboratory-confirmed dengue cases; 26 were locally acquired, constituting the largest outbreak in Texas since 2005. Because dengue outbreaks are expected to continue in south Texas and early case identification and timely treatment can reduce mortality, we sought to determine clinicians' knowledge of dengue and its clinical management. A survey was sent to 2,375 south Texas clinicians; 217 (9%) completed the survey. Approximately half of participants demonstrated knowledge needed to identify dengue cases, including symptoms (56%), early indicators of shock (54%), or timing of thrombocytopenia (48%). Fewer than 20% correctly identified all prevention messages, severe dengue warning signs, or circumstances in which a dengue patient should return for care. Knowledge of clinical management was limited; few participants correctly identified scenarios when plasma leakage occurred (10%) or a crystalloid solution was indicated (7%); however, 45% correctly identified when a blood transfusion was indicated. Because of the ongoing threat of dengue, we recommend clinicians in south Texas receive dengue clinical management training.

Biological Control of Mosquitoes in Scrap Tires in Brownsville, Texas, USA and Matamoros, Tamaulipas, Mexico
Journal of The American Mosquito Control Association, Jun 1, 2014
Dengue periodically circulates in southern Texas and neighboring Tamaulipas, Mexico; thus, a clos... more Dengue periodically circulates in southern Texas and neighboring Tamaulipas, Mexico; thus, a closer examination of human and vector ecology at the northern limits of North American transmission may improve prevention activities. Scrap tires produce large mosquito populations and increase the risk of dengue transmission. Some households choose not to pay tire disposal fees, and many tires are illegally dumped in residential areas. Biological control may provide low-cost and environmentally friendly mosquito control. This pilot study evaluated the ability of Mesocyclops longisetus to reduce mosquito populations in existing residential scrap tire piles. Mosquito populations were measured by the number of all mosquito pupae within tires or adult Aedes aegypti and Ae. albopictus near piles. Mesocyclops longisetus treated piles did not significantly reduce total mosquito pupae (P = 0.07) in Matamoros, Mexico. The study also evaluated the efficacy of native Toxorhynchites moctezuma which preferentially colonized tire piles under vegetation cover in Brownsville, TX. Toxorhynchites moctezuma larvae significantly reduced total mosquito pupae, but the strength of control diminished over time.

PLOS Neglected Tropical Diseases, Jun 13, 2022
Chikungunya virus (CHIKV) caused a large outbreak in Puerto Rico in 2014, followed by a Zika viru... more Chikungunya virus (CHIKV) caused a large outbreak in Puerto Rico in 2014, followed by a Zika virus (ZIKV) outbreak in 2016. Communities Organized for the Prevention of Arboviruses (COPA) is a cohort study in southern Puerto Rico, initiated in 2018 to measure arboviral disease risk and provide a platform to evaluate interventions. To identify risk factors for infection, we assessed prevalence of previous CHIKV infection and recent ZIKV and DENV infection in a cross-sectional study among COPA participants. Participants aged 1-50 years (y) were recruited from randomly selected households in study clusters. Each participant completed an interview and provided a blood specimen, which was tested by anti-CHIKV IgG ELISA assay and anti-ZIKV and anti-DENV IgM MAC-ELISA assays. We assessed individual, household, and community factors associated with a positive result for CHIKV or ZIKV after adjusting for confounders. During 2018-2019, 4,090 participants were enrolled; 61% were female and median age was 28y (interquartile range [IQR]: 16-41). Among 4,035 participants tested for CHIKV, 1,268 (31.4%) had evidence of previous infection. CHIKV infection prevalence was lower among children 1-10 years old compared to people 11 and older (adjusted odds ratio [aOR] 2.30; 95% CI 1.71-3.08). Lower CHIKV infection prevalence was associated with home screens (aOR 0.51; 95% CI 0.42-0.61) and air conditioning (aOR 0.64; 95% CI 0.54-0.77). CHIKV infection prevalence also varied by study cluster of residence and insurance type. Few participants (16; 0.4%) had evidence of recent DENV infection by IgM. Among 4,035 participants tested for ZIKV, 651 (16%) had evidence of recent infection. Infection prevalence increased with older age, from 7% among 1-10y olds up to 19% among 41-50y olds (aOR 3.23; 95% CI 2.16-4.84). Males had an increased risk of Zika infection prevalence compared with females (aOR 1.31; 95% CI 1.09-1.57). ZIKV infection prevalence also decreased with the presence of home screens (aOR 0.66; 95% CI 0.54-0.82) and air conditioning (aOR 0.69; 95% CI 0.57-0.84). Similar infection patterns were observed for recent ZIKV infection prevalence and previous CHIKV infection PLOS NEGLECTED TROPICAL DISEASES

American Journal of Tropical Medicine and Hygiene, Oct 7, 2015
We evaluated the use of federal public health intervention tools known as the Do Not Board and Bo... more We evaluated the use of federal public health intervention tools known as the Do Not Board and Border Lookout (BL) for detecting and referring infectious or potentially infectious land border travelers with tuberculosis (TB) back to treatment. We used data about the issuance of BL from April 2007 to September 2013 to examine demographics and TB laboratory results for persons on the list (N = 66) and time on the list before being located and achieving noninfectious status. The majority of case-patients were Hispanic and male, with a median age of 39 years. Most were citizens of the United States or Mexico, and 30.3% were undocumented migrants. One-fifth had multidrugresistant TB. Nearly two-thirds of case-patients were located and treated as a result of being placed on the list. However, 25.8% of case-patients, primarily undocumented migrants, remain lost to follow-up and remain on the list. For this highly mobile patient population, the use of this novel federal travel intervention tool facilitated the detection and treatment of infectious TB cases that were lost to follow-up.

Morbidity and Mortality Weekly Report, May 4, 2018
Introduction: Vectorborne diseases are major causes of death and illness worldwide. In the United... more Introduction: Vectorborne diseases are major causes of death and illness worldwide. In the United States, the most common vectorborne pathogens are transmitted by ticks or mosquitoes, including those causing Lyme disease; Rocky Mountain spotted fever; and West Nile, dengue, and Zika virus diseases. This report examines trends in occurrence of nationally reportable vectorborne diseases during 2004-2016. Methods: Data reported to the National Notifiable Diseases Surveillance System for 16 notifiable vectorborne diseases during 2004-2016 were analyzed; findings were tabulated by disease, vector type, location, and year. Results: A total 642,602 cases were reported. The number of annual reports of tickborne bacterial and protozoan diseases more than doubled during this period, from >22,000 in 2004 to >48,000 in 2016. Lyme disease accounted for 82% of all tickborne disease reports during 2004-2016. The occurrence of mosquitoborne diseases was marked by virus epidemics. Transmission in Puerto Rico, the U.S. Virgin Islands, and American Samoa accounted for most reports of dengue, chikungunya, and Zika virus diseases; West Nile virus was endemic, and periodically epidemic, in the continental United States. Conclusions and Implications for Public Health Practice: Vectorborne diseases are a large and growing public health problem in the United States, characterized by geographic specificity and frequent pathogen emergence and introduction. Differences in distribution and transmission dynamics of tickborne and mosquitoborne diseases are often rooted in biologic differences of the vectors. To effectively reduce transmission and respond to outbreaks will require major national improvement of surveillance, diagnostics, reporting, and vector control, as well as new tools, including vaccines.
Community perceptions on challenges and solutions to implement an Aedes aegypti control project in Ponce, Puerto Rico (USA)
PLOS ONE, Apr 17, 2023
US-Mexico binational COVID-19 cases in southern California border counties, California, February–June 2020
Journal of Migration and Health

American Journal of Public Health, 2019
The increasing geographical spread and disease incidence of arboviral infections are among the gr... more The increasing geographical spread and disease incidence of arboviral infections are among the greatest public health concerns in the Americas. The region has observed an increasing trend in dengue incidence in the last decades, evolving from low to hyperendemicity. Yellow fever incidence has also intensified in this period, expanding from sylvatic-restricted activity to urban outbreaks. Chikungunya started spreading pandemically in 2005 at an unprecedented pace, reaching the Americas in 2013. The following year, Zika also emerged in the region with an explosive outbreak, carrying devastating congenital abnormalities and neurologic disorders and becoming one of the greatest global health crises in years. The inadequate arbovirus surveillance in the region and the lack of serologic tests to differentiate among viruses poses substantial challenges. The evidence for vector control interventions remains weak. Clinical management remains the mainstay of arboviral disease control. Current...
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Papers by Stephen Waterman