Member, Maternal & Child Health Research Institute (MCHRI)
Plasmid-mediated antibiotic resistance among uropathogens in primigravid women-Hyderabad, India.
2020; 15 (5): e0232710
With the growing threat of antimicrobial resistance worldwide, uncovering the molecular epidemiology is critical for understanding what is driving this crisis. We aimed to evaluate the prevalence of plasmid-mediated-quinolone-resistance (PMQR) and extended-spectrum beta-lactamase- (ESBL) producing gram-negative organisms among primigravid women with bacteriuria. We collected urine specimens from primigravid women attending their first antenatal visit at Gandhi Hospital during October 1, 2015 to September 30, 2016. We determined antimicrobial susceptibility and ESBL and quinolone resistance using VITEK-2. We performed polymerase chain reaction amplification on resistant isolates for detection of ESBL-encoding genes (TEM, SHV, CTX-M) and PMQR genes (qnrA, qnrB, qnrD, qnrS, aac (6')-Ib-cr). Of 1,841 urine samples, 133 demonstrated significant bacterial growth with gram-negative bacilli accounting for 85% of isolates, including Escherichia coli (n = 79), Klebsiella pneumoniae (n = 29), Sphingomonas (n = 3), Enterobacter (n = 1), and Citrobacter (n = 1). We found 65% of E. coli isolates and 41% of K. pneumoniae isolates were ESBL positive. Of ESBL-positive isolates, the most common genes conferring resistance were TEM-1 (66.7%) followed by CTX-M-15 (33.3%). Fifty-seven percent of ESBL-positive E. coli also demonstrated resistance to quinolones with the most common PMQR genes being qnr-S (62.5%) and aac (6')-Ib-cr (37.5%). We did not find any resistance to quinolones among ESBL-positive K. pneumoniae isolates. Across different classes of antibiotics we found a strong clustering of multi-drug resistance in E. coli with over 45% of ESBL-positive isolates demonstrating resistance to at least three classes of antibiotics. This study emphasizes the high prevalence of plasmid-mediated ESBL and quinolone resistance in community-acquired urinary tract infections of primigravid women. The overall abundance of multi-drug-resistant isolates in this population is alarming and may present therapeutic challenges.
View details for DOI 10.1371/journal.pone.0232710
View details for PubMedID 32384111
Zika Virus infection and Guillain-Barré syndrome in Northeastern Mexico: A case-control study.
2020; 15 (3): e0230132
Beginning August 2017, we conducted a prospective case-control investigation in Monterrey, Mexico to assess the association between Zika virus (ZIKV) and Guillain-Barré syndrome (GBS).For each of 50 GBS case-patients, we enrolled 2-3 afebrile controls (141 controls in total) matched by sex, age group, and presentation to same hospital within 7 days.PCR results for ZIKV in blood and/or urine were available on all subjects; serum ZIKV IgM antibody for 52% of case-patients and 80% of controls. Subjects were asked about antecedent illness in the two months prior to neurological onset (for case-patients) or interview (for controls). Laboratory evidence of ZIKV infection alone (PCR+ or IgM+) was not significantly different between case-patients and controls (OR: 1.26, 95% CI: 0.45-3.54) but antecedent symptomatic ZIKV infection [a typical ZIKV symptom (rash, joint pain, or conjunctivitis) plus laboratory evidence of ZIKV infection] was higher among case-patients (OR: 12.45, 95% CI: 1.45-106.64). GBS case-patients with laboratory evidence of ZIKV infection were significantly more likely to have had typical ZIKV symptoms than controls with laboratory evidence of ZIKV infection (OR: 17.5, 95% CI: 3.2-96.6). This association remained significant even when only GBS case-patients who were afebrile for 5 days before onset were included in the analysis, (OR 9.57 (95% CI: 1.07 to 85.35).During ZIKV epidemics, this study indicates that increases in GBS will occur primarily among those with antecedent symptomatic ZIKV.
View details for DOI 10.1371/journal.pone.0230132
View details for PubMedID 32214354
- Protecting front line health care workers should be the top priority in low-resource health systems: case of Bangladesh. Infection control and hospital epidemiology 2020: 1–7
Seroprevalence and Risk Factors Possibly Associated with Emerging Zoonotic Vaccinia Virus in a Farming Community, Colombia
EMERGING INFECTIOUS DISEASES
2019; 25 (12): 2169–76
In 2014, vaccinia virus (VACV) infections were identified among farmworkers in Caquetá Department, Colombia; additional cases were identified in Cundinamarca Department in 2015. VACV, an orthopoxvirus (OPXV) used in the smallpox vaccine, has caused sporadic bovine and human outbreaks in countries such as Brazil and India. In response to the emergence of this disease in Colombia, we surveyed and collected blood from 134 farmworkers and household members from 56 farms in Cundinamarca Department. We tested serum samples for OPXV antibodies and correlated risk factors with seropositivity by using multivariate analyses. Fifty-two percent of farmworkers had OPXV antibodies; this percentage decreased to 31% when we excluded persons who would have been eligible for smallpox vaccination. The major risk factors for seropositivity were municipality, age, smallpox vaccination scar, duration of time working on a farm, and animals having vaccinia-like lesions. This investigation provides evidence for possible emergence of VACV as a zoonosis in South America.
View details for DOI 10.3201/eid2512.181114
View details for Web of Science ID 000504030700001
View details for PubMedID 31743085
View details for PubMedCentralID PMC6874243
Long-term outcomes of Guillain-Barré syndrome possibly associated with Zika virus infection.
2019; 14 (8): e0220049
This prospective cohort investigation analyzed the long-term functional and neurologic outcomes of patients with Zika virus-associated Guillain-Barré syndrome (GBS) in Barranquilla, Colombia.Thirty-four Zika virus-associated GBS cases were assessed a median of 17 months following acute GBS illness. We assessed demographics, results of Overall Disability Sum Scores (ODSS), Hughes Disability Score (HDS), Zung Depression Scale (ZDS), and Health Related Quality of Life (HRQL) questionnaires; and compared outcomes indices with a normative sample of neighborhood-selected control subjects in Barranquilla without GBS.Median age at time of acute neurologic onset was 49 years (range, 10-80); 17 (50%) were male. No deaths occurred. At long-term follow-up, 25 (73%) patients had a HDS 0-1, indicating complete / near complete recovery. Among the group, HDS (mean 1.4, range 0-4), ODSS (mean 1.9, range 0-9) and ZDS score (mean 34.4, range 20-56) indicated mild / moderate ongoing disability. Adjusting for age and sex, Zika virus-associated GBS cases were similar to a population comparison group (n = 368) in Barranquilla without GBS in terms of prevalence of physical or mental health complaints, though GBS patients were more likely to have an ODSS of ≥ 1 (OR 8.8, 95% CI 3.2-24.5) and to suffer from moderate / moderate-severe depression (OR 3.89, 95% CI 1.23-11.17) than the comparison group.Long-term outcomes of Zika virus-associated GBS are consistent with those associated with other antecedent antigenic stimuli in terms of mortality and ongoing long-term morbidity, as published in the literature. Persons with Zika virus-associated GBS more frequently reported disability and depression after approximately one year compared with those without GBS.
View details for DOI 10.1371/journal.pone.0220049
View details for PubMedID 31369576
- Beta-Glucanemia after Coronary Artery Bypass Graft Surgery: A Case Report JOURNAL OF FUNGI 2018; 4 (4)
Beta-Glucanemia after Coronary Artery Bypass Graft Surgery: A Case Report.
Journal of fungi (Basel, Switzerland)
2018; 4 (4)
Blood salvage techniques are increasingly being used during surgical procedures to reduce the need for exogenous blood products. The blood recovered from the surgical field through aspiration or absorption by surgical sponges is reinfused into a patient. A 65-year old patient who underwent coronary artery bypass grafting using blood salvage techniques developed a fever on post-op day 3 and was noted to have an elevated beta-d-glucan level, a marker of systemic fungal infections. Ultimately, no fungal infection was identified, beta-d-glucan levels slowly decreased and the patient demonstrated clinical improvement. To determine whether blood salvage procedures led to his elevated beta-d-glucan levels, the surgical sponges were tested for elutable levels of beta-d-glucan. The beta-d-glucan content of the eluents was measured using the Fungitell IVD kit (Associates of Cape Cod, Inc.; East Falmouth, MA). The beta-d-glucan levels were found to be in concentrations 10,000-times greater than the limit of detection for human serum. While various studies have demonstrated both the immunomodulatory and pro-inflammatory effects of beta-d-glucan, the physiologic impact of such high levels of beta-d-glucan post-operatively remains unknown. Additionally, the persistence of detectable beta-d-glucan up to several weeks after surgical procedures presents a challenge for the diagnosis of invasive fungal infections. Further studies are needed to assess the beta-glucanemia-related safety of surgical materials and their potential biological effects.
View details for PubMedID 30279391
Use of the revised World Health Organization cluster survey methodology to classify measles-rubella vaccination campaign coverage in 47 counties in Kenya, 2016.
2018; 13 (7): e0199786
To achieve measles elimination, two doses of measles-containing vaccine (MCV) are provided through routine immunization services or vaccination campaigns. In May 2016, Kenya conducted a measles-rubella (MR) vaccination campaign targeting 19 million children aged 9 months-14 years, with a goal of achieving ≥95% coverage. We conducted a post-campaign cluster survey to estimate national coverage and classify coverage in Kenya's 47 counties.The stratified multi-stage cluster survey included data from 20,011 children in 8,253 households sampled using the recently revised World Health Organization coverage survey methodology (2015). Point estimates and 95% confidence intervals (95% CI) of national campaign coverage were calculated, accounting for study design. County vaccination coverage was classified as 'pass,' 'fail,' or 'intermediate,' using one-sided hypothesis tests against a 95% threshold.Estimated national MR campaign coverage was 95% (95% CI: 94%-96%). Coverage differed significantly (p < 0.05) by child's school attendance, mother's education, household wealth, and other factors. In classifying coverage, 20 counties passed (≥95%), two failed (<95%), and 25 were intermediate (unable to classify either way). Reported campaign awareness among caretakers was 92%. After the 2016 MR campaign, an estimated 93% (95% CI: 92%-94%) of children aged 9 months to 14 years had received ≥2 MCV doses; 6% (95% CI: 6%-7%) had 1 MCV dose; and 0.7% (95% CI: 0.6%-0.9%) remained unvaccinated.Kenya reached the MR campaign target of 95% vaccination coverage, representing a substantial achievement towards increasing population immunity. High campaign awareness reflected the comprehensive social mobilization strategy implemented in Kenya and supports the importance of including strong communications platforms in future vaccination campaigns. In counties with sub-optimal MR campaign coverage, further efforts are needed to increase MCV coverage to achieve the national goal of measles elimination by 2020.
View details for DOI 10.1371/journal.pone.0199786
View details for PubMedID 29965975
View details for PubMedCentralID PMC6028100
A Comparison of the Quality of Informed Consent for Clinical Trials of an Experimental Hookworm Vaccine Conducted in Developed and Developing Countries.
PLoS neglected tropical diseases
2017; 11 (1): e0005327
Informed consent is one of the principal ethical requirements of conducting clinical research, regardless of the study setting. Breaches in the quality of the informed consent process are frequently described in reference to clinical trials conducted in developing countries, due to low levels of formal education, a lack of familiarity with biomedical research, and limited access to health services in these countries. However, few studies have directly compared the quality of the informed consent process in developed and developing countries using the same tool and in similar clinical trials. This study was conducted to compare the quality of the informed consent process of a series of clinical trials of an investigational hookworm vaccine that were performed in Brazil and the United States. A standardized questionnaire was used to assess the ethical quality of the informed consent process in a series of Phase 1 clinical trials of the Na-GST-1/Alhydrogel hookworm vaccine that were conducted in healthy adults in Brazil and the United States. In Brazil, the trial was conducted at two sites, one in the hookworm non-endemic urban area of Belo Horizonte, Minas, and one in the rural, resource-limited town of Americaninhas, both in the state of Minas Gerais; the American trial was conducted in Washington, DC. A 32-question survey was administered after the informed consent document was signed at each of the three trial sites; it assessed participants' understanding of information about the study presented in the document as well as the voluntariness of their decision to participate. 105 participants completed the questionnaire: 63 in Americaninhas, 18 in Belo Horizonte, and 24 in Washington, DC. Overall knowledge about the trial was suboptimal: the mean number of correct answers to questions about study objectives, methods, duration, rights, and potential risks and benefits, was 45.6% in Americaninhas, 65.2% in Belo Horizonte, and 59.1% in Washington, DC. Although there was no difference in the rate of correct answers between participants in Belo Horizonte and Washington, DC, there was a significant gap between participants at these two locations compared to Americaninhas (p = 0.0002 and p = 0.0001, respectively), which had a lower percentage of correct answers. Attitudes towards participating in the clinical trial also differed by site: while approximately 40% had doubts about participating in Washington, DC and Belo Horizonte, only 1.5% had concerns in Americaninhas. Finally, in Belo Horizonte and Washington, high percentages cited a desire to help others as motivation for participating, whereas in Americaninhas, the most common reason for participating was personal interest (p = 0.001). Understanding of information about a Phase 1 clinical trial of an experimental hookworm vaccine following informed consent was suboptimal, regardless of study site. Although overall there were no differences in knowledge between Brazil and the US, a lower level of understanding about the trial was seen in participants at the rural, resource-limited Brazilian site. These findings demonstrate the need for educational interventions directed at potential clinical trial participants, both in developing and developed countries, in order to improve understanding of the informed consent document.
View details for DOI 10.1371/journal.pntd.0005327
View details for PubMedID 28114401
View details for PubMedCentralID PMC5289607
Human Rabies - Puerto Rico, 2015.
MMWR. Morbidity and mortality weekly report
2017; 65 (52): 1474–76
On December 1, 2015, the Puerto Rico Department of Health (PRDH) was notified by a local hospital of a suspected human rabies case. The previous evening, a Puerto Rican man aged 54 years arrived at the emergency department with fever, difficulty swallowing, hand paresthesia, cough, and chest tightness. The next morning the patient left against medical advice but returned to the emergency department in the afternoon with worsening symptoms. The patient's wife reported that he had been bitten by a mongoose during the first week of October, but had not sought care for the bite. While being transferred to the intensive care unit, the patient went into cardiac arrest and died. On December 3, rabies was confirmed from specimens collected during autopsy. PRDH conducted an initial rapid risk assessment, and five family members were started on rabies postexposure prophylaxis (PEP).
View details for DOI 10.15585/mmwr.mm6552a4
View details for PubMedID 28056006
Incidence and clinical characteristics of Guillain-Barré syndrome before the introduction of Zika virus in Puerto Rico.
Journal of the neurological sciences
2017; 377: 102–6
Zika virus has been associated with increases in Guillain-Barré syndrome (GBS) incidence. A GBS incidence estimation and clinical description was performed to assess baseline GBS epidemiology before the introduction of Zika virus in Puerto Rico.Hospitalization administrative data from an island-wide insurance claims database and U.S. Census Bureau population estimates provided a crude GBS incidence for 2013. This estimate was adjusted using the proportion of GBS cases meeting Brighton criteria for confirmed GBS from nine reference hospitals. Characteristics of confirmed GBS cases in the same nine hospitals during 2012-2015 are described.A total of 136 GBS hospitalization claims were filed in 2013 (crude GBS incidence was 3.8 per 100,000 population). The adjusted GBS incidence was 1.7 per 100,000 population. Of 67 confirmed GBS cases during 2012-2015, 66% had an antecedent illness. Median time from antecedent illness to GBS onset was 7days. Most cases (67%) occurred during July-September.Puerto Rico's GBS incidence for 2013 was estimated using a combination of administrative data and medical records review; this method could be employed in other regions to monitor GBS incidence before and after the introduction of GBS infectious triggers.
View details for PubMedID 28477675
Increased rates of Guillain-Barré syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil.
PLoS neglected tropical diseases
2017; 11 (8): e0005869
In mid-2015, Salvador, Brazil, reported an outbreak of Guillain-Barré syndrome (GBS), coinciding with the introduction and spread of Zika virus (ZIKV). We found that GBS incidence during April-July 2015 among those ≥12 years of age was 5.6 cases/100,000 population/year and increased markedly with increasing age to 14.7 among those ≥60 years of age. We conducted interviews with 41 case-patients and 85 neighborhood controls and found no differences in demographics or exposures prior to GBS-symptom onset. A higher proportion of case-patients (83%) compared to controls (21%) reported an antecedent illness (OR 18.1, CI 6.9-47.5), most commonly characterized by rash, headache, fever, and myalgias, within a median of 8 days prior to GBS onset. Our investigation confirmed an outbreak of GBS, particularly in older adults, that was strongly associated with Zika-like illness and geo-temporally associated with ZIKV transmission, suggesting that ZIKV may result in severe neurologic complications.
View details for DOI 10.1371/journal.pntd.0005869
View details for PubMedID 28854206
View details for PubMedCentralID PMC5595339
Zika virus disease-associated Guillain-Barré syndrome-Barranquilla, Colombia 2015-2016.
Journal of the neurological sciences
2017; 381: 272–77
An outbreak of Guillain-Barré syndrome (GBS), a disorder characterized by acute, symmetric limb weakness with decreased or absent deep-tendon reflexes, was reported in Barranquilla, Colombia, after the introduction of Zika virus in 2015. We reviewed clinical data for GBS cases in Barranquilla and performed a case-control investigation to assess the association of suspect and probable Zika virus disease with GBS.We used the Brighton Collaboration Criteria to confirm reported GBS patients in Barranquilla during October 2015-April 2016. In April 2016, two neighborhood and age range-matched controls were selected for each confirmed GBS case-patient. We obtained demographics and antecedent symptoms in the 2-month period before GBS onset for case-patients and the same period for controls. Sera were collected for Zika virus antibody testing. Suspected Zika virus disease was defined as a history of rash and ≥2 other Zika-related symptoms (fever, arthralgia, myalgia, or conjunctivitis). Probable Zika virus disease was defined as suspected Zika virus disease with laboratory evidence of a recent Zika virus or flavivirus infection. Conditional logistic regression adjusted for sex and race/ethnicity was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).We confirmed 47 GBS cases. Incidence increased with age (10-fold higher in those ≥60years versus those <20years). We interviewed 40 case-patients and 79 controls. There was no significant difference in laboratory evidence of recent Zika virus or flavivirus infection between case-patients and controls (OR: 2.2; 95% CI: 0.9-5.1). GBS was associated with having suspected (OR: 3.0, 95% CI: 1.1-8.6) or probable Zika virus disease (OR: 4.6, CI: 1.1-19.0).Older individuals and those with suspected and probable Zika virus disease had higher odds of developing GBS.We confirmed a Guillain-Barré syndrome (GBS) outbreak in Barranquilla, Colombia, during October 2015-April 2016. A case-control investigation using neighborhood controls showed an association of suspected and probable Zika virus disease with GBS.
View details for PubMedID 28991697
Human Rabies - Wyoming and Utah, 2015.
MMWR. Morbidity and mortality weekly report
2016; 65 (21): 529–33
In September 2015, a Wyoming woman was admitted to a local hospital with a 5-day history of progressive weakness, ataxia, dysarthria, and dysphagia. Because of respiratory failure, she was transferred to a referral hospital in Utah, where she developed progressive encephalitis. On day 8 of hospitalization, the patient's family told clinicians they recalled that, 1 month before admission, the woman had found a bat on her neck upon waking, but had not sought medical care. The patient's husband subsequently had contacted county invasive species authorities about the incident, but he was not advised to seek health care for evaluation of his wife's risk for rabies. On October 2, CDC confirmed the patient was infected with a rabies virus variant that was enzootic to the silver-haired bat (Lasionycteris noctivagans). The patient died on October 3. Public understanding of rabies risk from bat contact needs to be improved; cooperation among public health and other agencies can aid in referring persons with possible bat exposure for assessment of rabies risk.
View details for DOI 10.15585/mmwr.mm6521a1
View details for PubMedID 27253630
In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate.
2015; 12: 132
Copper has antimicrobial properties and has been studied for its activity against viruses, including HIV. Copper complexed within a phthalocyanine ring, forming copper (II) phthalocyanine sulfate (CuPcS), may have a role in microbicide development when used intravaginally.CuPcS toxicity was tested against cervical epithelial cells, TZM-BL cells, peripheral blood mononuclear cells (PBMC), and cervical explant tissues using cell viability assays. In vivo toxicity was assessed following intravaginal administration of CuPcS in female BALB/C mice and measured using a standardized histology grading system on reproductive tract tissues. Efficacy studies for preventing infection with HIV in the presence of various non-toxic concentrations of CuPcS were carried out in TZM-BL, PBMC, and cervical explant cultures using HIV-1BAL and various pseudovirus subtypes. Non-linear regression was applied to the data to determine the EC50/90 and CC50/90.CuPcS demonstrated inhibition of HIV infection in PBMCs at concentrations that were non-toxic in cervical epithelial cells and PBMCs with EC50 values of approximately 50 μg/mL. Reproductive tract tissue analysis revealed no toxicity at 100 mg/mL. Human cervical explant tissues challenged with HIV in the presence of CuPcS also revealed a dose-response effect at preventing HIV infection at non-toxic concentrations with an EC50 value of 65 μg/mL.These results suggest that CuPcS may be useful as a topical microbicide in concentrations that can be achieved in the female genital tract.
View details for DOI 10.1186/s12985-015-0358-5
View details for PubMedID 26319137
View details for PubMedCentralID PMC4552998
- A HISTORY OF MICROBICIDES AND THEIR CURRENT DEVELOPMENT PIPELINE DRUGS OF THE FUTURE 2011; 36 (12): 909–18