Screening the United States Blood Supply for West Nile Virus: A Question of Blood, Dollars, and Sense

Lee and Biggerstaff discuss two new studies on the cost effectiveness of different strategies for screening blood for West Nile virus

binGroup2: Statistical Tools for Infection Identification via Group Testing

Group testing is the process of testing items as an amalgamation, rather than separately, to determine the binary status for each item. Its use was especially important during the COVID-19 pandemic through testing specimens for SARS-CoV-2. The adoption of group testing for this and many other applications is because members of a negative testing group can be declared negative with potentially only one test. This subsequently leads to significant increases in laboratory testing capacity. Whenever a group testing algorithm is put into practice, it is critical for laboratories to understand the algorithm’s operating characteristics, such as the expected number of tests. Our paper presents the binGroup2 package that provides the statistical tools for this purpose. This R package is the first to address the identification aspect of group testing for a wide variety of algorithms. We illustrate its use through COVID-19 and chlamydia/gonorrhea applications of group testing

West Nile Virus–associated Flaccid Paralysis Outcome

We report 1-year follow-up data from a longitudinal prospective cohort study of patients with West Nile virus–associated paralysis. As in the 4-month follow-up, a variety of recovery patterns were observed, but persistent weakness was frequent. Respiratory involvement was associated with considerable illness and death

Risk Estimation of Sexual Transmission of Zika Virus-United States, 2016-2017

BACKGROUND: Zika virus (ZIKV) can be transmitted sexually but the risk of sexual transmission remains unknown. Most evidence of sexual transmission is from partners of infected travelers returning from areas with ZIKV circulation. METHODS: We used data from the US national arboviral disease surveillance system on travel- and sexually acquired ZIKV disease cases during 2016-2017 to develop individual-level simulations for estimating risk of male-to-female, male-to-male, and female-to-male sexual transmission of ZIKV via vaginal and/or anal intercourse. We specified parametric distributions to characterize individual-level variability of parameters for ZIKV persistence and sexual behaviors. RESULTS: Using ZIKV RNA persistence in semen/vaginal fluids to approximate infectiousness duration, male-to-male transmission had the highest estimated probability (1.3% [95% confidence interval, CI, .4%-6.0%] per anal sex act), followed by male-to-female and female-to-male transmission (0.4% [95% CI, .3%-.6%] per vaginal/anal sex act and 0.1% [95% CI, 0%-.8%] per vaginal sex act, respectively). Models using viral isolation in semen vs RNA detection to approximate infectiousness duration predicted greater risk of sexual transmission. CONCLUSIONS: While likely insufficient to maintain sustained transmission, the estimated risk of ZIKV transmission through unprotected sex is not trivial and is especially important for pregnant women, as ZIKV infection can cause severe congenital disorders

Rapid West Nile Virus Antigen Detection

We compared the VecTest WNV antigen assay with standard methods of West Nile virus (WNV) detection in swabs from American Crows (Corvus brachyrhynchos) and House Sparrows (Passer domesticus). The VecTest detected WNV more frequently than the plaque assay and was comparable to a TaqMan reverse transcription–polymerase chain reaction

West Nile Virus–associated Flaccid Paralysis

The causes and frequency of acute paralysis and respiratory failure with West Nile virus (WNV) infection are incompletely understood. During the summer and fall of 2003, we conducted a prospective, population-based study among residents of a 3-county area in Colorado, United States, with developing WNV-associated paralysis. Thirty-two patients with developing paralysis and acute WNV infection were identified. Causes included a poliomyelitislike syndrome in 27 (84%) patients and a Guillain-Barré–like syndrome in 4 (13%); 1 had brachial plexus involvement alone. The incidence of poliomyelitislike syndrome was 3.7/100,000. Twelve patients (38%), including 1 with Guillain-Barré–like syndrome, had acute respiratory failure that required endotracheal intubation. At 4 months, 3 patients with respiratory failure died, 2 remained intubated, 25 showed various degrees of improvement, and 2 were lost to followup. A poliomyelitislike syndrome likely involving spinal anterior horn cells is the most common mechanism of WNV-associated paralysis and is associated with significant short- and long-term illness and death

On the Treatment of Airline Travelers in Mathematical Models

The global spread of infectious diseases is facilitated by the ability of infected humans to travel thousands of miles in short time spans, rapidly transporting pathogens to distant locations. Mathematical models of the actual and potential spread of specific pathogens can assist public health planning in the case of such an event. Models should generally be parsimonious, but must consider all potentially important components of the system to the greatest extent possible. We demonstrate and discuss important assumptions relative to the parameterization and structural treatment of airline travel in mathematical models. Among other findings, we show that the most common structural treatment of travelers leads to underestimation of the speed of spread and that connecting travel is critical to a realistic spread pattern. Models involving travelers can be improved significantly by relatively simple structural changes but also may require further attention to details of parameterization

Infection and Transmission of Rift Valley Fever Viruses Lacking the NSs and/or NSm Genes in Mosquitoes: Potential Role for NSm in Mosquito Infection

Rift Valley fever virus is transmitted mainly by mosquitoes and causes disease in humans and animals throughout Africa and the Arabian Peninsula. The impact of disease is large in terms of human illness and mortality, and economic impact on the livestock industry. For these reasons, and because there is a risk of this virus spreading to Europe and North America, it is important to develop a vaccine that is stable, safe and effective in preventing infection. Potential vaccine viruses have been developed through deletion of two genes (NSs and NSm) affecting virus virulence. Because this virus is normally transmitted by mosquitoes we must determine the effects of the deletions in these vaccine viruses on their ability to infect and be transmitted by mosquitoes. An optimal vaccine virus would not infect or be transmitted. The viruses were tested in two mosquito species: Aedes aegypti and Culex quinquefasciatus. Deletion of the NSm gene reduced infection of Ae. aegypti mosquitoes indicating a role for the NSm protein in mosquito infection. The virus with deletion of both NSs and NSm genes was the best vaccine candidate since it did not infect Ae. aegypti and showed reduced infection and transmission rates in Cx. quinquefasciatus

Discussion of “Is group testing ready for prime-time in disease Identification?” by Haber, Malinovsky, and Albert, Statistics in Medicine, 2021

I congratulate the authors on an interesting, instructive, and timely paper. Certainly, including the testing for SARS-CoV-2 example in a paper on a topic—group testing—of wide interest during the current COVID-19 pandemic emphasizes the relevance of the topic in public health and diagnostic medicine generally. But the thoughtful inclusion of the remaining examples—HIV, HPV, and cancer biomarker detection—illustrates that the issues considered are important even in less urgent times. In this note of discussion I will comment on two particular aspects in the paper that I found particularly informative, and then I will comment on two other, related areas that I believe the conclusions inform. I found the direct use of explicit constraints on Se(k) and Sp(k) in design optimization natural and, as the authors say, “very easy to interpret and explain to non-statisticians.” Incorporating these constraints at the outset of design optimization should have the further, philosophical advantage that consideration of and specification of these must (ideally) be made by subject matter experts before cost evaluations are undertaken, so that screening and diagnostic needs rather than cost constraints do not unduly drive (or result in inadvertant or active manipulation of) performance requirements

Estimated risk of transmission of the West Nile virus through blood transfusion in the US, 2002

BACKGROUND: The West Nile virus (WNV) epidemic in 2002 in the US saw over 3300 reported human cases of WNV disease, with over 2300 reported cases of WNV encephalitis and meningitis. The first documented cases of transfusion transmission of WNV through voluntary blood donation also occurred. STUDY DESIGN AND METHODS: Case onset dates from the 2002 WNV epidemic in the US were used to estimate the risk of transfusion-associated transmission with statistical resampling. An easily computed approximating formula for the mean risk was derived. Estimates were computed for six high-incidence states and metropolitan areas. RESULTS: Mean and maximum risk of transfusion associated WNV transmission (per 10,000 donations) during the epidemic period for the selected states ranged from 2.12 to 4.76 and from 4.34 to 10.46, respectively; for the selected metropolitan areas, they ranged from 1.46 to 12.33 and from 3.02 to 21.32, respectively. CONCLUSIONS: Estimates of the mean risk of WNV transmission by transfusion ranged from 1.46 to 12.33 per 10,000 donations for six high-incidence metropolitan areas during the 2002 epidemic. Because the risk was highly geographically and temporally variable, computation of geographically localized estimates is recommended. The derived approximating formula for the mean risk performed well for the estimates given