Rebecca S. B. Fischer

Clinical Evidence of Acute Mesoamerican Nephropathy.

Mesoamerican nephropathy (MeN), an epidemic of unexplained kidney disease in Central America, affects mostly young, healthy individuals. Its etiology is a mystery that requires urgent investigation. Largely described as a chronic kidney disease (CKD), no acute clinical scenario has been characterized. An understanding of the early disease process could elucidate an etiology and guide treatment and prevention efforts. We sought to document the earliest clinical signs in patients with suspected MeN in a high-risk population in Nicaragua. Physicians at a local hospital identified suspect cases and documented clinical/laboratory data, demographics, and medical histories. Over a 1-year period, physicians identified 255 mostly young (median 29 years), male (89.5%) patients with elevated creatinine or reduced creatinine clearance. Mean serum creatinine (2.0 ± 0.6 mg/dL) revealed a 2-fold increase from baseline, and half had stage 2 or 3 acute kidney injury. Leukocyturia (98.4%), leukocytosis (81.4%), and neutrophilia (86.2%) predominated. Nausea (59.4%), back pain (57.9%), fever (54.6%), vomiting (50.4%), headache (47.3%), and muscle weakness (45.0%) were common. A typical case of acute MeN presented with elevated (or increased ≥ 0.3 mg/dL or ≥ 1.5-fold from baseline) creatinine, no hypertension or diabetes, leukocyturia, and at least two of fever, nausea or vomiting, back pain, muscle weakness, headache, or leukocytosis and/or neutrophilia. Rapid progression (median 90 days) to CKD was recorded in 8.5% of patients. This evidence can serve as the basis of a sensitive and urgently needed case definition for disease surveillance of early-stage, acute MeN.

Early detection of acute tubulointerstitial nephritis in the genesis of Mesoamerican nephropathy

Mesoamerican nephropathy is a devastating disease of unknown etiology that affects mostly young agricultural workers in Central America. An understanding of the mechanism of injury and the early disease process is urgently needed and will aid in identification of the underlying cause and direct treatment and prevention efforts. We sought to describe the renal pathology in Mesoamerican nephropathy at its earliest clinical appearance in prospectively identified acute case patients in Nicaragua. We considered those with elevated (or increased at least 0.3 mg/dL or 1.5-fold from baseline) serum creatinine, leukocyturia, and either leukocytosis or neutrophilia for inclusion in this biopsy study. Renal tissue was obtained by ultrasound-guided biopsy for examination by light, immunofluorescence, and electron microscopy. All 11 individuals who underwent renal biopsy showed tubulointerstitial nephritis, with varying degrees of inflammation and chronicity. Interstitial cellular infiltrates (predominantly T lymphocytes and monocytes), mostly in the corticomedullary junction; neutrophilic accumulation in the tubular lumens; largely preserved glomeruli; few mild ischemic changes; and no immune deposits were noted. The acute components of tubulointerstitial nephritis were acute tubular cell injury, interstitial edema, and early fibrosis. Chronic tubulointerstitial nephritis included severe tubular atrophy, thickened tubular basement membrane, and interstitial fibrosis. Thus, renal histopathology in Mesoamerican nephropathy reveals primary interstitial disease with intact glomeruli.

Genome-Wide Association Study of Staphylococcus aureus Carriage in a Community-Based Sample of Mexican-Americans in Starr County, Texas.

Staphylococcus aureus is the number one cause of hospital-acquired infections. Understanding host pathogen interactions is paramount to the development of more effective treatment and prevention strategies. Therefore, whole exome sequence and chip-based genotype data were used to conduct rare variant and genome-wide association analyses in a Mexican-American cohort from Starr County, Texas to identify genes and variants associated with S. aureus nasal carriage. Unlike most studies of S. aureus that are based on hospitalized populations, this study used a representative community sample. Two nasal swabs were collected from participants (n = 858) 11–17 days apart between October 2009 and December 2013, screened for the presence of S. aureus, and then classified as either persistent, intermittent, or non-carriers. The chip-based and exome sequence-based single variant association analyses identified 1 genome-wide significant region (KAT2B) for intermittent and 11 regions suggestively associated with persistent or intermittent S. aureus carriage. We also report top findings from gene-based burden analyses of rare functional variation. Notably, we observed marked differences between signals associated with persistent and intermittent carriage. In single variant analyses of persistent carriage, 7 of 9 genes in suggestively associated regions and all 5 top gene-based findings are associated with cell growth or tight junction integrity or are structural constituents of the cytoskeleton, suggesting that variation in genes associated with persistent carriage impact cellular integrity and morphology.

Staphylococcus aureus nasal colonization among HIV-infected adults in Botswana: prevalence and risk factors

ABSTRACT We sought to determine the clinical and epidemiologic determinants of Staphylococcus aureus nasal colonization in HIV-infected individuals at two outpatient centers in southern Botswana. Standard microbiologic techniques were used to identify S. aureus and methicillin-resistant S. aureus (MRSA). In a sample of 404 HIV-infected adults, prevalence of S. aureus nasal carriage was 36.9% (n = 152) and was associated with domestic overcrowding and lower CD4 cell count. MRSA prevalence was low (n = 13, 3.2%), but more common among individuals with asthma and eczema. The implications of these findings for HIV management are discussed.

Arboviral Surveillance among Pediatric Patients with Acute Febrile Illness in Houston, Texas

We instituted active surveillance among febrile patients presenting to the largest Houston-area pediatric emergency department to identify acute infections of dengue virus (DENV), West Nile virus (WNV), and chikungunya virus (CHIKV). In 2014, 1,063 children were enrolled, and 1,015 (95%) had blood and/or cerebrospinal fluid specimens available for DENV, WNV, and CHIKV testing. Almost half (49%) reported recent mosquito bites, and 6% (N = 60) reported either recent international travel or contact with an international traveler. None were positive for acute WNV; three had false-positive CHIKV results; and two had evidence of DENV. One DENV-positive case was an acute infection associated with international travel, whereas the other was identified as a potential secondary acute infection, also likely travel-associated. Neither of the DENV-positive cases were clinically recognized, highlighting the need for education and awareness. Health-care professionals should consider the possibility of arboviral disease among children who have traveled to or from endemic areas.

Challenges to Diagnosing Leptospirosis in Endemic Regions Require Urgent Attention

Purpose of ReviewLeptospirosis is one of the most widespread zoonotic diseases, poses health and economic threats across the globe, yet little investment in tools to identify and eliminate disease have been made.Recent FindingsCurrent gold standard diagnostics are time-intensive, suffer sensitivity and specificity challenges, and are scarce in resource-limited settings, where the largest disease burden exists. Central American countries are at higher risk than most of the world, although challenges to surveillance limit our understanding of the true impact of leptospirosis on that region. One of the greatest challenges to surveillance is the laboratory capacity and technical expertise to accurately and quickly diagnose disease.SummaryThere is an immediate need for a redesign of the testing algorithm for leptospirosis in order to improve surveillance and inform treatment and prevention activities. A global collaboration to increase laboratory capacity in Central America that includes improved access to technologies beyond the current gold standard is important to explore.

Leptospirosis in Central America: Techniques for Diagnosis and Molecular Characterization

Purpose of ReviewLeptospirosis is a zoonotic disease caused by pathogenic spirochetes of the genus Leptospira. In Central America, Leptospira is endemic, and almost all countries experience frequent outbreaks. Diagnosis of leptospirosis is primarily based on serology. More technologically advanced methods, such as polymerase chain reaction (PCR), are used in only a few laboratories, although it can identify genes specific to pathogenic species. New techniques, such as isothermal reactions and molecular typing could also contribute to disease surveillance in humans, animals, and the environment.Recent FindingsAdvanced techniques, including molecular characterization methods, have been used only rarely up until now. In Nicaragua, we have used phenotypic analysis to characterize pathogenic Leptospira species and multiple locus sequence typing (MLST) to facilitate the identification of a completely new serovar in Costa Rica.SummaryImproved technology and expertise for molecular typing of Leptospira are needed in order to improve surveillance and provide the basis for epidemiologic studies. Current MLST characterization schemes include representative strains known to be circulating in Central America, and a more widespread implementation of this technique could enrich information about the epidemiology of Leptospira and enable identification of novel strains emerging in the region.

Prevalence of Staphylococcus aureus Nasal Carriage in Human Immunodeficiency Virus–Infected and Uninfected Children in Botswana: Prevalence and Risk Factors

AbstractStaphylococcus aureus is an important cause of morbidity and mortality in children in sub-Saharan Africa (SSA). A major risk factor for staphylococcal infection is S. aureus colonization of the anterior nares. We sought to define risk factors for S. aureus carriage and characterize antimicrobial resistance patterns in children in Botswana. A cross-sectional study was conducted at two clinical sites in southern Botswana. Patients under 18 years of age underwent two nasal swabs and brief interviews, 4 weeks apart. Standard microbiological techniques were used. For persistent carriers, S. aureus was isolated from swabs at both time points, and for intermittent carriers, S. aureus was isolated from only one swab. Poisson regression with robust variance estimator was used to compare prevalence of carriage and the resistance phenotypes. Among 56 enrollees, prevalence of S. aureus colonization was 55% (N = 31), of whom 42% (N = 13) were persistent carriers. Of human immunodeficiency virus-infected children, 64% (N = 9) were carriers. Risk factors for nasal carriage included a history of tuberculosis (prevalence ratio [PR] = 1.60; 95% confidence interval [CI] = 1.02, 2.51; P = 0.040) and closer proximity to health care (PR = 0.89; 95% CI = 0.80, 0.99; P = 0.048). Prior pneumonia was more common among persistent rather than intermittent carriers (PR = 2.64; 95% CI = 1.64, 4.23; P < 0.001). Methicillin-resistant S. aureus (MRSA) prevalence was 13%. Of isolates tested, 16% were resistant to three or more drugs (N = 7/44). In summary, children in southern Botswana are frequently colonized with S. aureus. Antibiotic resistance, especially MRSA, is also widespread. Antibiotic recommendations for treatment of staphylococcal infections in SSA should take cognizance of these resistance patterns.