Coccidioidomycosis Seroincidence and Risk among Military Personnel, Naval Air Station Lemoore, San Joaquin Valley, California, USA1.

We conducted a retrospective cohort study that tested 2,000 US military personnel for Coccidioides antibodies in a disease-endemic region. The overall incidence of seroconversion was 0.5 cases/100 person-years; 12.5% of persons who seroconverted had illnesses requiring medical care. No significant association was found between demographic characteristics and seroconversion or disease.

Human Adenovirus Type 55 Distribution, Regional Persistence, and Genetic Variability.

Human adenovirus type 55 (HAdV-55) causes acute respiratory disease of variable severity and has become an emergent threat in both civilian and military populations. HAdV-55 infection is endemic to China and South Korea, but data from other regions and time periods are needed for comprehensive assessment of HAdV-55 prevalence from a global perspective. In this study, we subjected HAdV-55 isolates from various countries collected during 1969-2018 to whole-genome sequencing, genomic and proteomic comparison, and phylogenetic analyses. The results show worldwide distribution of HAdV-55; recent strains share a high degree of genomic homogeneity. Distinct strains circulated regionally for several years, suggesting persistent local transmission. Several cases of sporadic introduction of certain strains to other countries were documented. Among the identified amino acid mutations distinguishing HAdV-55 strains, some have potential impact on essential viral functions and may affect infectivity and transmission.

Chemoprophylaxis against group A streptococcus during military training.

Chemoprophylaxis with intramuscular benzathine penicillin G has been used widely by the U.S. military to prevent epidemics of group A streptococcus infections during basic training. The recent global shortage of benzathine penicillin prompted a detailed analysis of this issue in 2017 by military preventive medicine and infectious disease authorities in San Antonio, Texas, and San Diego, California, USA. This paper explores the history of group A streptococcus and chemoprophylaxis in the U.S. military training environment, current policy and practice, and challenges associated with widespread chemoprophylaxis. In light of the history presented, preventive medicine authorities at basic training centers should be extremely cautious about discontinuing benzathine penicillin chemoprophylaxis.

Pott's disease? AIDS-associated Mycobacterium heckeshornense spinal osteomyelitis and diskitis.

Acid-fast bacillus (AFB) spinal osteomyelitis in a patient with AIDS is often presumed to be caused by reactivated Mycobacterium tuberculosis. However, other AFB pathogens can mimic M. tuberculosis and, to ensure appropriate and adequate therapy, should be considered by clinicians. We present a case of aggressive spinal osteomyelitis caused by Mycobacterium heckeshornense in an AIDS patient; a review of the literature is also included.

Genetic variation and recurrent parasitaemia in Peruvian Plasmodium vivax populations.

BACKGROUND: Plasmodium vivax is a predominant species of malaria in parts of South America and there is increasing resistance to drugs to treat infections by P. vivax. The existence of latent hypnozoites further complicates the ability to classify recurrent infections as treatment failures due to relapse, recrudescence of hyponozoites or re-infections. Antigen loci are putatively under natural selection and may not be an optimal molecular marker to define parasite haplotypes in paired samples. Putatively neutral microsatellite loci, however, offer an assessment of neutral haplotypes. The objective here was to assess the utility of neutral microsatellite loci to reconcile cases of recurrent parasitaemia in Amazonian P. vivax populations in Peru. METHODS: Patient blood samples were collected from three locations in or around Iquitos in the Peruvian Amazon. Five putatively neutral microsatellite loci were characterized from 445 samples to ascertain the within and amongst population variation. A total of 30 day 0 and day of recurrent parasitaemia samples were characterized at microsatellite loci and five polymorphic antigen loci for haplotype classification. RESULTS: The genetic diversity at microsatellite loci was consistent with neutral levels of variation measured in other South American P. vivax populations. Results between antigen and microsatellite loci for the 30 day 0 and day of recurrent parasitaemia samples were the same for 80% of the pairs. The majority of non-concordant results were the result of differing alleles at microsatellite loci. This analysis estimates that 90% of the paired samples with the same microsatellite haplotype are unlikely to be due to a new infection. CONCLUSIONS: A population-level approach was used to yield a better estimate of the probability of a new infection versus relapse or recrudescence of homologous hypnozoites; hypnozoite activation was common for this cohort. Population studies are critical with the evaluation of genetic markers to assess P. vivax biology and epidemiology. The additional demonstration of microsatellite loci as neutral markers capable of distinguishing the origin of the recurrent parasites (new infection or originating from the patient) lends support to their use in assessment of treatment outcomes.

The redox-switch domain of Hsp33 functions as dual stress sensor.

The redox-regulated chaperone Hsp33 is specifically activated upon exposure of cells to peroxide stress at elevated temperatures. Here we show that Hsp33 harbors two interdependent stress-sensing regions located in the C-terminal redox-switch domain of Hsp33: a zinc center sensing peroxide stress conditions and an adjacent linker region responding to unfolding conditions. Neither of these sensors works sufficiently in the absence of the other, making the simultaneous presence of both stress conditions a necessary requirement for Hsp33's full activation. Upon activation, Hsp33's redox-switch domain adopts a natively unfolded conformation, thereby exposing hydrophobic surfaces in its N-terminal substrate-binding domain. The specific activation of Hsp33 by the oxidative unfolding of its redox-switch domain makes this chaperone optimally suited to quickly respond to oxidative stress conditions that lead to protein unfolding.

Malaria and other vector-borne infection surveillance in the U.S. Department of Defense Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance program: review of 2009 accomplishments.

Vector-borne infections (VBI) are defined as infectious diseases transmitted by the bite or mechanical transfer of arthropod vectors. They constitute a significant proportion of the global infectious disease burden. United States (U.S.) Department of Defense (DoD) personnel are especially vulnerable to VBIs due to occupational contact with arthropod vectors, immunological naiveté to previously unencountered pathogens, and limited diagnostic and treatment options available in the austere and unstable environments sometimes associated with military operations. In addition to the risk uniquely encountered by military populations, other factors have driven the worldwide emergence of VBIs. Unprecedented levels of global travel, tourism and trade, and blurred lines of demarcation between zoonotic VBI reservoirs and human populations increase vector exposure. Urban growth in previously undeveloped regions and perturbations in global weather patterns also contribute to the rise of VBIs. The Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) and its partners at DoD overseas laboratories form a network to better characterize the nature, emergence and growth of VBIs globally. In 2009 the network tested 19,730 specimens from 25 sites for Plasmodium species and malaria drug resistance phenotypes and nearly another 10,000 samples to determine the etiologies of non-Plasmodium species VBIs from regions spanning from Oceania to Africa, South America, and northeast, south and Southeast Asia. This review describes recent VBI-related epidemiological studies conducted by AFHSC-GEIS partner laboratories within the OCONUS DoD laboratory network emphasizing their impact on human populations.

A prospective observational study describing severity of acquired diarrhea among U.S. military and Western travelers participating in the Global Travelers' Diarrhea Study.

BACKGROUND: Travelers' diarrhea (TD) is one of the most common illnesses affecting modern-day travelers, including military personnel. Previous work has shown that afflicted travelers may alter their itineraries and be confined to bed rest due to symptoms, and military personnel may become incapable of completing operational requirements. Examination of signs, symptoms, and severity of diarrheagenic pathogens can inform clinical diagnosis and prioritization of future surveillance and research activities. METHODS: Utilizing a global laboratory network, culture and molecular testing were performed in parallel at each site on a group of core pathogens, and definitions for acute diarrhea (AD), severe AD, acute gastroenteritis (AGE), and severe AGE were determined using data elements in the modified Vesikari scale. We included 210 cases of TD reporting all variables of interest in our severity assessment analysis. RESULTS: Out of all cases, 156/210 (74%) met criteria for severe AD and 35/210 (17%) for severe AGE. Examination of severity by pathogen revealed that, at non-military sites, 17/19 (89%) of enteropathogenic Escherichia coli (E. coli) (EPEC) infections, 28/32 (88%) of enterotoxigenic E. coli (ETEC) infections, and 13/15 (87%) of Shigella/enteroinvasive E. coli (EIEC) infections resulted in severe AD cases. At the military site, all infections of ETEC (6/6), Shigella-EIEC (4/4), and enteroaggregative E. coli (EAEC) resulted in AD. Norovirus infections at non-military and military sites resulted in 27% (14/51) and 33% (3/9) severe AGE cases, respectively. CONCLUSIONS: This study found a high percentage of participants enrolled at both military and non-military sites experienced severe AD with concerning numbers of severe cases at non-military sites reporting hospitalization and reductions in performance. Since travelers with mild TD symptoms are less likely to present to health care workers than those with more severe TD, there is a potential selection bias in this study that may have overestimated the proportion of more severe outcomes among all individuals who could have participated in the GTD study. Future research should examine other covariates among pathogen and host, such as treatment and comorbid conditions, that may contribute to the presence of signs and symptoms and their severity.

Live Oral Adenovirus Type 4 and Type 7 Vaccine Induces Durable Antibody Response.

Human adenoviruses (AdV) are mostly associated with minimal pathology. However, more severe respiratory tract infections and acute respiratory diseases, most often caused by AdV-4 and AdV-7, have been reported. The only licensed vaccine in the United States, live oral AdV-4 and AdV-7 vaccine, is indicated for use in the military, nearly exclusively in recruit populations. The excellent safety profile and prominent antibody response of the vaccine is well established by placebo-controlled clinical trials, while, long-term immunity of vaccination has not been studied. Serum samples collected over 6 years from subjects co-administered live oral AdV-4 and AdV-7 vaccine in 2011 were evaluated to determine the duration of the antibody response. Group geometric mean titers (GMT) at 6 years post vaccination compared to previous years evaluated were not significantly different for either AdV-4 or AdV-7 vaccine components. There were no subjects that demonstrated waning neutralization antibody (NAb) titers against AdV-4 and less than 5% of subjects against AdV-7. Interestingly, there were subjects that had a four-fold increase in NAb titers against either AdV-4 or AdV-7, at various time points post vaccination, suggesting either homotypic or heterotypic re-exposure. This investigation provided strong evidence that the live oral AdV-4 and AdV-7 vaccine induced long-term immunity to protect from AdV-4 and AdV-7 infections.

A Multisite Network Assessment of the Epidemiology and Etiology of Acquired Diarrhea among U.S. Military and Western Travelers (Global Travelers' Diarrhea Study): A Principal Role of Norovirus among Travelers with Gastrointestinal Illness.

U.S. military personnel must be ready to deploy to locations worldwide, including environments with heightened risk of infectious disease. Diarrheal illnesses continue to be among the most significant infectious disease threats to operational capability. To better prevent, detect, and respond to these threats and improve synchronization across the Department of Defense (DoD) overseas laboratory network, a multisite Global Travelers' Diarrhea protocol was implemented with standardized case definitions and harmonized laboratory methods to identify enteric pathogens. Harmonized laboratory procedures for detection of Norovirus (NoV), enterotoxigenic Escherichia coli (ETEC), enteroaggregative E. coli, Shiga toxin-producing E. coli, enteropathogenic E. coli, Salmonella enterica, Shigella/enteroinvasive E. coli, and Campylobacter jejuni have been implemented at six DoD laboratories with surveillance sites in Egypt, Honduras, Peru, Nepal, Thailand, and Kenya. Samples from individuals traveling from wealthy to poorer countries were collected between June 2012 and May 2018, and of samples with all variables of interest available (n = 410), most participants enrolled were students (46%), tourists (26%), U.S. military personnel (13%), or other unspecified travelers (11%). One or more pathogens were detected in 59% of samples tested. Of samples tested, the most commonly detected pathogens were NoV (24%), ETEC (16%), and C. jejuni (14%), suggesting that NoV plays a larger role in travelers' diarrhea than has previously been described. Harmonized data collection and methods will ensure identification and characterization of enteric pathogens are consistent across the DoD laboratory network, ultimately resulting in more comparable data for global assessments, preventive measures, and treatment recommendations.

Shewanella algae Infections in United States Naval Special Warfare Trainees.

Shewanella infections are uncommon in immunocompetent hosts. We report 6 cases of Shewanella algae infection in young, healthy Naval Special Warfare trainees in San Diego during 2 consecutive El Niño seasons, defining a unique population at risk and adding to the epidemiologic understanding of this potentially virulent organism.

Prevalence of seropositivity to spotted fever group rickettsiae and Anaplasma phagocytophilum in a large, demographically diverse US sample.

BACKGROUND: Most epidemiologic studies of tick-borne rickettsial diseases in the United States are small and have limited demographic scope, making broader risk assessment difficult. METHODS: We conducted a seroprevalence study of spotted fever group rickettsiae and Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis. Specimens were selected randomly from the Department of Defense Serum Repository for 10,000 diverse military personnel at various stages in their careers who were serving with active duty status in 1997. Antibody testing included enzyme-linked immunosorbent assay for Rickettsia rickettsii and A. phagocytophilum, and Western blot confirmation for A. phagocytophilum. Risk factors were assessed using logistic regression. RESULTS: Subjects were mostly male and young and were diverse ethnically and geographically. Spotted fever group rickettsiae seropositivity was 6.0% (95% confidence interval, 5.5%-6.4%). In univariable logistic regression, seroprevalence was significantly higher among older subjects, men (6.5%, compared with 3.3% among women), black individuals (8.7%, compared with 5.6% among white individuals), subjects from states with above-average Rocky Mountain spotted fever incidence, and subjects in ground combat specialties. Associations remained significant in multivariable analysis for age, sex, black versus white race, home state with high incidence, and ground combat specialty. Among 696 subjects with serum samples obtained within 7 days after entering the military, the rate of seropositivity was 3.4% (95% confidence interval, 2.1%-4.8%). Seroprevalence was nonsignificantly lower in men (3.4%, compared with 3.7% in women ) and in black individuals (3.4%, compared with 4.1% in white individuals). A. phagocytophilum seropositivity, as determined by by enzyme-linked immunosorbent assay and Western blot, was 2.6% and 0.11% (95% confidence interval, 0.05%-0.18%), respectively. Western blot seropositivity was not significantly associated with subject characteristics in univariable analysis. CONCLUSIONS: Spotted fever group rickettsiae exposure was common and A. phagocytophilum exposure was rare in a US population with broad demographic diversity.

Surveillance for norovirus and enteric bacterial pathogens as etiologies of acute gastroenteritis at U.S. military recruit training centers, 2011-2016.

An estimated 179 million cases of acute gastroenteritis (AGE) occur each year in the U.S. and AGE is commonly reported within both training and deployed U.S. military populations. Beginning in 2011, the Operational Infectious Diseases laboratory at Naval Health Research Center (NHRC) has undertaken routine surveillance of four U.S. military training facilities to systematically track the prevalence of AGE and to establish its etiologies among U.S. military recruits. Employing both molecular and standard microbiological techniques, NHRC routinely assays for pathogens of direct military relevance, including norovirus genogroups I and II, Salmonella, Shigella, and Campylobacter. During its initial surveillance efforts (2011-2016), NHRC identified norovirus as the primary etiology of both sporadic cases and outbreaks of AGE among trainees.

Genetic Variability of Plasmodium vivax in the North Coast of Peru and the Ecuadorian Amazon Basin.

In the Peruvian North Coast (PNC), the number of Plasmodium vivax malaria cases increased steadily from 2007 to 2010 despite a significant decline in the overall number of cases in Peru during the same period. To better understand the transmission dynamics of P. vivax populations in the PNC and the neighboring Ecuadorian Amazon Basin (EAB), we studied the genetic variability and population structure of P. vivax in these areas. One hundred and twenty P. vivax isolates (58 from Piura and 37 from Tumbes in the PNC collected from 2008 to 2010 and 25 from the EAB collected in Pastaza from 2001 to 2004) were assessed by five polymorphic microsatellite markers. Genetic variability was determined by expected heterozygosity (He) and population structure by Bayesian inference cluster analysis. We found very low genetic diversity in the PNC (He = 0-0.32) but high genetic diversity in the EAB (He = 0.43-0.70). Population structure analysis revealed three distinct populations in the three locations. Six of 37 (16%) isolates from Tumbes had an identical haplotype to that found in Piura, suggesting unidirectional flow from Piura to Tumbes. In addition, one haplotype from Tumbes showed similarity to a haplotype found in Pastaza, suggesting that this could be an imported case from EAB. These findings strongly suggest a minimal population flow and different levels of genetic variability between these two areas divided by the Andes Mountains. This work presents molecular markers that could be used to increase our understanding of regional malaria transmission dynamics, which has implications for the development of strategies for P. vivax control.

Zinc center as redox switch--new function for an old motif.

Oxidative stress affects a wide variety of different cellular processes. Now, an increasing number of proteins have been identified that use the presence of reactive oxygen species or alterations in the cellular thiol-disulfide state as regulators of their protein function. This review focuses on two members of this growing group of redox-regulated proteins that utilize a cysteine-containing zinc center as the redox switch: Hsp33, the first molecular chaperone, whose ability to protect cells against stress-induced protein unfolding depends on the presence of reactive oxygen species and RsrA, the first anti-sigma factor that uses a cysteine-containing zinc center to sense and respond to cellular disulfide stress.

The crystal structure of the reduced, Zn2+-bound form of the B. subtilis Hsp33 chaperone and its implications for the activation mechanism.

The bacterial heat shock protein Hsp33 is a redox-regulated chaperone activated by oxidative stress. In response to oxidation, four cysteines within a Zn2+ binding C-terminal domain form two disulfide bonds with concomitant release of the metal. This leads to the formation of the biologically active Hsp33 dimer. The crystal structure of the N-terminal domain of the E. coli protein has been reported, but neither the structure of the Zn2+ binding motif nor the nature of its regulatory interaction with the rest of the protein are known. Here we report the crystal structure of the full-length B. subtilis Hsp33 in the reduced form. The structure of the N-terminal, dimerization domain is similar to that of the E. coli protein, although there is no domain swapping. The Zn2+ binding domain is clearly resolved showing the details of the tetrahedral coordination of Zn2+ by four thiolates. We propose a structure-based activation pathway for Hsp33.

Outbreak of Cutaneous Leishmaniasis in Peruvian Military Personnel Undertaking Training Activities in the Amazon Basin, 2010.

Military personnel deployed to the Amazon Basin are at high risk for cutaneous leishmaniasis (CL). We responded to an outbreak among Peruvian Army personnel returning from short-term training in the Amazon, conducting active case detection, lesion sample collection, and risk factor assessment. The attack rate was 25% (76/303); the incubation period was 2-36 weeks (median = 8). Most cases had one lesion (66%), primarily ulcerative (49%), and in the legs (57%). Real-time polymerase chain reaction (PCR) identified Leishmania (Viannia) braziliensis (59/61 = 97%) and L. (V.) guyanensis (2/61 = 3%). Being male (risk ratio [RR] = 4.01; P = 0.034), not wearing long-sleeve clothes (RR = 1.71; P = 0.005), and sleeping in open rooms (RR = 1.80; P = 0.009) were associated with CL. Sodium stibogluconate therapy had a 41% cure rate, less than previously reported in Peru (~70%; P < 0.001). After emphasizing pre-deployment education and other basic prevention measures, trainees in the following year had lower incidence (1/278 = 0.4%; P < 0.001). Basic prevention can reduce CL risk in deployed militaries.

Needs, acceptability, and value of humanitarian medical assistance in remote Peruvian Amazon riverine communities.

Much debate exists regarding the need, acceptability, and value of humanitarian medical assistance. We conducted a cross-sectional study on 457 children under 5 years from four remote riverine communities in the Peruvian Amazon and collected anthropometric measures, blood samples (1-4 years), and stool samples. Focus groups and key informant interviews assessed perspectives regarding medical aid delivered by foreigners. The prevalence of stunting, anemia, and intestinal parasites was 20%, 37%, and 62%, respectively. Infection with multiple parasites, usually geohelminths, was detected in 41% of children. The prevalence of intestinal parasites both individual and polyparasitism increased with age. Participants from smaller communities less exposed to foreigners expressed lack of trust and fear of them. However, participants from all communities were positive about foreigners visiting to provide health support. Prevalent health needs such as parasitic infections and anemia may be addressed by short-term medical interventions. There is a perceived openness to and acceptability of medical assistance delivered by foreign personnel.