Coralith García

Noroviruses as a Cause of Traveler's Diarrhea among Students from the United States Visiting Mexico

ABSTRACT Stool specimens from 124 international travelers with acute diarrhea were tested for the presence of enteropathogens. Noroviruses (NoVs) were the second most commonly identified enteric pathogen in diarrheal stool samples (21/124, 17%), exceeded only by enterotoxigenic Escherichia coli (50/106, 47%). This study indicates that NoV is an underappreciated cause of travelers diarrhea.

Vitamin A Supplementation Has Divergent Effects on Norovirus Infections and Clinical Symptoms among Mexican Children

BACKGROUND The effect of vitamin A supplementation on viral gastrointestinal infections among young children living in developing countries remains unclear. METHODS The effect of vitamin A supplementation on norovirus (NoV) infection among 127 Mexican children 5-15 months of age was studied in a randomized, placebo-controlled trial during June-August 1998. Stool samples collected every 2 weeks and after diarrheal episodes were screened for NoV and characterized at the genogroup level (GI and GII). RESULTS Of the stool samples collected, 29.9% were positive for NoV, and NoV GI and NoV GII were found in 55.4% and 46.4% of the positive samples, respectively. Vitamin A supplementation reduced the prevalence of NoV GII infections (rate ratio [RR], 0.60 [95% confidence interval {CI}, 0.20-0.82]), increased the length of both NoV GI and GII shedding, and decreased the prevalence of NoV-associated diarrhea (RR, 0.51 [95% CI, 0.26-0.97]). CONCLUSIONS These findings suggest that NoV is an important cause of pediatric diarrhea in this study population and that vitamin A supplementation has divergent effects on specific outcomes of NoV infection.

Efficacy of sulfadoxine-pyrimethamine and mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria in the Amazon basin of Peru

In vivo antimalarial drug efficacy studies of uncomplicated Plasmodium falciparum malaria at an isolated site in the Amazon basin of Peru bordering Brazil and Colombia showed >50% RII/RIII resistance to sulfadoxine-pyrimethamine but no evidence of resistance to mefloquine.

Use of Ivermectin to Treat an Institutional Outbreak of Scabies in a Low-Resource Setting

In a limited-resource hospital in Lima, Peru, 23 (63.9%) of 36 healthcare workers developed pruritus and/or skin lesions after contact with a patient with classic scabies. Of these 23, a total of 5 healthcare workers had scabies confirmed by microscopy. Oral ivermectin was used to control the outbreak effectively.

Vitamin A Modifies the Intestinal Chemokine and Cytokine Responses to Norovirus Infection in Mexican Children

Vitamin A supplementation is associated with divergent clinical norovirus (NoV) outcomes in Mexican children. Fecal cytokine concentrations following NoV genogroup infections among 127 Mexican children 5-15 mo old enrolled in a randomized, double-blind, placebo-controlled, vitamin A supplementation trial were determined to clarify the role the gut immune response plays in these associations. Stools collected from supplemented children [20,000 IU retinol (3.3 IU = 1 μg retinol) for children < 12 mo of age; 45,000 iu for children ≥ 12 mo] or children in the placebo group were screened for NoV genogroups I (GI) and II (GII). Monocyte chemoattractant protein-1 (MCP-1), TNFα, IL-5, IL-6, IL-8, IL-4, IFNγ, and IL-10 fecal concentrations were also determined. Differences in cytokine levels between the 2 groups following GI and GII infections were determined using ordered logistic regression models. MCP-1 and IL-8 levels were greater among GI- and GII-infected children, respectively, compared with uninfected children, whereas IL-5 levels were greater following both genogroup infections. MCP-1, IL-8, and IL-6 fecal levels were reduced among supplemented children with GII-associated diarrhea compared with the placebo group. Vitamin A-supplemented, GII-infected children had reduced MCP-1 and TNFα levels compared with GII-infected children in the placebo group (P-interaction = 0.02 and 0.03, respectively). Supplemented children with GI-associated diarrhea had higher TNFα and IL-4 levels compared with children in the placebo group with diarrhea (P-interaction = 0.02 and 0.02, respectively). The divergent effects of supplementation on NoV outcomes may result from the different effects vitamin A has on the genogroup-specific immune responses.

Antimicrobial Drug Resistance in Peru

To the Editor: In Latin American countries, rates of antimicrobial drug resistance among bacterial pathogens are high. Data on these rates in Peru are incomplete (1), and no institution in Peru has participated in multinational surveillance studies (2–4). To document the antimicrobial drug resistance profile of key pathogens, we organized a surveillance network of clinical laboratories from 9 hospitals (public, general, tertiary care, and quaternary care) in Lima, the capital of Peru. Over a 12-month period (April 2008–March 2009), we consecutively collected positive bacterial blood culture isolates (other than coagulase-negative staphylococci) from each of the 9 hospitals. Only the first isolate per patient was included. Patients’ age and hospital ward were recorded. Identification and susceptibility testing were performed at the Institute of Tropical Medicine Alexander von Humboldt (Lima, Peru). Staphylococcus aureus was identified by conventional methods, and susceptibility testing was conducted by oxacillin salt agar screening and disk diffusion (5). For gram-negative bacilli, including extended-spectrum β-lactamases (ESBL), identification and susceptibility testing were performed by conventional techniques and by MicroScan NC50 panels (Dade-Behring, West Sacramento, CA, USA) (5). American Type Culture Collection strains were used as controls. During the study period, we collected 1,681 unique isolates. We report the first 934 isolates tested from the more common species collected (375 Staphylococcus aureus, 321 Klebsiella pneumoniae, 125 Escherichia coli, and 113 Pseudomonas aeruginosa). Overall, S. aureus was the most frequently recovered species, accounting for 22.0% of organisms. Of 375 S. aureus isolates tested, 244 (65.0%) were methicillin resistant (MRSA) and 131 were methicillin susceptible. MRSA frequency was highest among isolates from intensive care units (ICUs) (61 [68.5%] of 89 isolates), but it was also high among isolates from emergency wards (55 [57.3%] of 96 isolates); this difference did not reach statistical significance. Among the 244 MRSA isolates, 170 (69.6%) were also co-resistant to the combination of ciprofloxacin, gentamicin, and clindamycin; rates of co-resistance did not differ significantly among MRSA isolates from patients in the emergency ward (32/55, 58.2%) and those from patients in ICUs and hospital wards (133/184, 72.3%, p = 0.67). Among the 131 methicillin-susceptible isolates, resistance rates were as follows: ciprofloxacin (5.3%), gentamicin (10.7%), clindamycin (14.5%), and erythromycin (14.5%). All S. aureus isolates were susceptible to linezolid, teicoplanin, and vancomycin; clindamycin-inducible resistance was found in 10 (38.5%) of 26 isolates resistant to erythromycin and apparently susceptible to clindamycin. K. pneumoniae was the second most frequently recovered organism, accounting for 19.1% of organisms collected. Among 321 K. pneumoniae isolates tested, 241 (75.1%) produced ESBL, 207 (64.5%) showed resistance to ciprofloxacin, and 233 (72.6%) were resistant to trimethoprim-sulfamethoxazole; proportions did not differ among age groups, wards, or hospitals. Of the 241 ESBL-producing isolates, 136 (56.4%) showed co-resistance to ciprofloxacin and gentamicin and 66 (27.4%) were also resistant to amikacin. Of the 80 non–ESBL-producing isolates, 37 (46.3%) were resistant to ciprofloxacin. All K. pneumoniae isolates retained susceptibility to imipenem and meropenem. A large proportion of K. pneumoniae infections were suspected to have been hospital acquired because most (280/321, 87.2%) were recovered from patients already hospitalized, including one third (96/321, 29.9%) of those from the neonatal ward. Although K. pneumoniae occasionally caused microepidemics in neonatal wards, most isolates were recovered randomly over time and from different hospitals. Among 125 E. coli isolates tested, 96 (76.8%) produced ESBL, 107 (85.6%) were resistant to ciprofloxacin, and 108 (86.4%) were resistant to trimethoprim-sulfamethoxazole. The resistance rate to ciprofloxacin was higher among adults than children (90.5% vs. 60.0%, p = 0.002). Of 96 ESBL-positive isolates, 59 (61.5%) were co-resistant to gentamicin and ciprofloxacin but only 9 (9.4%) were resistant to amikacin. Among 29 non–ESBL-producing E. coli isolates, 19 (65.5%) were resistant to ciprofloxacin. All isolates were susceptible to imipenem and meropenem. We hypothesized that the high level of E. coli resistance to ciprofloxacin may be related to community overuse of fluorquinolones for common infections, such as acute diarrhea. Among 113 P. aeruginosa isolates tested, 62 (54.8%) came from patients in ICUs and 73 (64.0%) were isolated from adults. Multidrug-resistance (defined as resistance to at least 3 of the following: ciprofloxacin, imipenem, amikacin, ceftazidime) was found for 67 (59.3%) of the 133 isolates, more among adults (65.7%) than among children (43.2%, p = 0.024). Overall, 34.5% were resistant to piperacilin-tazobactam. Our main study limitation was not having complete clinical and epidemiologic information to define which isolates were acquired in the hospital and which were acquired in the community. Overall, rates of antimicrobial drug resistance among common pathogens in hospitals of Lima, Peru, were high.

Staphylococcus aureus causing tropical pyomyositis, Amazon Basin, Peru.

We studied 12 Staphylococcus aureus isolates causing tropical pyomyositis in the Amazon Basin of Peru. All isolates were methicillin-susceptible; 11 carried Panton-Valentine leukocidin–encoding genes, and 5 belonged to multilocus sequence type 25 and possessed an extensive set of enterotoxins. Our findings suggest sequence type 25 is circulating in tropical areas of South America.

High Frequency of Diarrheagenic Escherichia coli in Human Immunodeficiency Virus (HIV) Patients with and without Diarrhea in Lima, Perú

Diarrhea is still a prevalent health issue in HIV patients. Our objective was to characterize the different diarrheagenic E. coli (DEC) groups in stools from adult HIV patients. Cross sectional study: We enrolled HIV-positive and -negative patients with and without diarrhea from a tertiary-care center of Lima, Peru. Clinical data was recorded and a stool sample per patient was cultured. Multiplex PCR was used to detect different DECs. One hundred eighty-four participants were enrolled. The frequency of having at least one DEC was more common in HIV-positive than HIV-negative patients with diarrhea (42% versus 20%, P < 0.05). The enterotoxigenic E. coli (ETEC) was the most common DEC in patients with diarrhea, 13% in HIV patients. The diffusely adherent E. coli (DAEC) was only present in HIV positive patients with diarrhea (10.1%). Different types of DEC are frequent in stools from HIV-positive patients.

Effects of Point Mutations in Plasmodium falciparum Dihydrofolate Reductase and Dihydropterate Synthase Genes on Clinical Outcomes and In Vitro Susceptibility to Sulfadoxine and Pyrimethamine

Background Sulfadoxine-pyrimethamine was a common first line drug therapy to treat uncomplicated falciparum malaria, but increasing therapeutic failures associated with the development of significant levels of resistance worldwide has prompted change to alternative treatment regimes in many national malaria control programs. Methodology and Finding We conducted an in vivo therapeutic efficacy trial of sulfadoxine-pyrimethamine at two locations in the Peruvian Amazon enrolling 99 patients of which, 86 patients completed the protocol specified 28 day follow up. Our objective was to correlate the presence of polymorphisms in P. falciparum dihydrofolate reductase and dihydropteroate synthase to in vitro parasite susceptibility to sulfadoxine and pyrimethamine and to in vivo treatment outcomes. Inhibitory concentration 50 values of isolates increased with numbers of mutations (single [108N], sextuplet [BR/51I/108N/164L and 437G/581G]) and septuplet (BR/51I/108N/164L and 437G/540E/581G) with geometric means of 76 nM (35–166 nM), 582 nM (49-6890- nM) and 4909 (3575–6741 nM) nM for sulfadoxine and 33 nM (22–51 nM), 81 nM (19–345 nM), and 215 nM (176–262 nM) for pyrimethamine. A single mutation present in the isolate obtained at the time of enrollment from either dihydrofolate reductase (164L) or dihydropteroate synthase (540E) predicted treatment failure as well as any other single gene alone or in combination. Patients with the dihydrofolate reductase 164L mutation were 3.6 times as likely to be treatment failures [failures 85.4% (164L) vs 23.7% (I164); relative risk = 3.61; 95% CI: 2.14 – 6.64] while patients with the dihydropteroate synthase 540E were 2.6 times as likely to fail treatment (96.7% (540E) vs 37.5% (K540); relative risk = 2.58; 95% CI: 1.88 – 3.73). Patients with both dihydrofolate reductase 164L and dihydropteroate synthase 540E mutations were 4.1 times as likely to be treatment failures [96.7% vs 23.7%; RR = 4.08; 95% CI: 2.45 – 7.46] compared to patients having both wild forms (I164 and K540). Conclusions In this part of the Amazon basin, it may be possible to predict treatment failure with sulfadoxine-pyrimethamine equally well by determination of either of the single mutations dihydrofolate reductase 164L or dihydropteroate synthase 540E. Trial Registration ClinicalTrials.gov NCT00951106 NCT00951106

A Prospective Cohort Multicenter Study of Molecular Epidemiology and Phylogenomics of Staphylococcus aureus Bacteremia in Nine Latin American Countries

ABSTRACT Staphylococcus aureus is an important pathogen causing a spectrum of diseases ranging from mild skin and soft tissue infections to life-threatening conditions. Bloodstream infections are particularly important, and the treatment approach is complicated by the presence of methicillin-resistant S. aureus (MRSA) isolates. The emergence of new genetic lineages of MRSA has occurred in Latin America (LA) with the rise and dissemination of the community-associated USA300 Latin American variant (USA300-LV). Here, we prospectively characterized bloodstream MRSA recovered from selected hospitals in 9 Latin American countries. All isolates were typed by pulsed-field gel electrophoresis (PFGE) and subjected to antibiotic susceptibility testing. Whole-genome sequencing was performed on 96 MRSA representatives. MRSA represented 45% of all (1,185 S. aureus) isolates. The majority of MRSA isolates belonged to clonal cluster (CC) 5. In Colombia and Ecuador, most isolates (≥72%) belonged to the USA300-LV lineage (CC8). Phylogenetic reconstructions indicated that MRSA isolates from participating hospitals belonged to three major clades. Clade A grouped isolates with sequence type 5 (ST5), ST105, and ST1011 (mostly staphylococcal chromosomal cassette mec [SCCmec] I and II). Clade B included ST8, ST88, ST97, and ST72 strains (SCCmec IV, subtypes a, b, and c/E), and clade C grouped mostly Argentinian MRSA belonging to ST30. In summary, CC5 MRSA was prevalent in bloodstream infections in LA with the exception of Colombia and Ecuador, where USA300-LV is now the dominant lineage. Clonal replacement appears to be a common phenomenon, and continuous surveillance is crucial to identify changes in the molecular epidemiology of MRSA.