Long-term prognosis of idiopathic ventricular fibrillation: An eighteen-year experience from a tertiary center.

INTRODUCTION AND OBJECTIVES: Idiopathic ventricular fibrillation (IVF) is diagnosed in patients who survive sudden cardiac arrest (SCA), preferably with documented ventricular fibrillation (VF), without any identifiable structural or electrical abnormality. Current evidence provides limited guidance on the diagnosis and follow-up of these patients. Our aim was to assess the clinical outcomes of survivors of an aborted SCA attributed to IVF. METHODS: We retrospectively collected clinical data from all patients who survived SCA and implanted a cardiac defibrillator (ICD) between 2005 and 2023. RESULTS: A total of 38 patients, 36.8% female, with a mean age of 44±14 years old were included. Median follow-up time was 8.7 years (interquartile range (IQR) 4.7-14.7 years). All patients underwent a comprehensive diagnostic evaluation that excluded structural and coronary disease. During follow-up, underlying diagnoses were established in 34.2% of the whole cohort. Genetic testing, performed in 37.2%, revealed underlying diagnoses in 57.1% of those tested, compared to only 26.3% of patients who did not undergo genetic testing [p=0.035, OR=5.1 (95% confidence interval (CI) 1.2-21.5)]. Mortality was 10.5% (due to non-arrhythmic causes) and 36.8% patients received appropriate therapies with a median time to first ICD therapy of 39 [5.4-47.3] months. CONCLUSION(S): Etiological diagnosis and recurrence prediction in patients with IVF remains challenging, even with extensive diagnostic evaluation and long-term follow-up. In our study, genetic testing enhanced diagnostic yield. Consistent with previous findings, our cohort experienced a notable arrhythmic recurrence, with no cardiac deaths, underlining the pivotal role of ICD implantation in these patients.

Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a Portuguese hospital.

Background: Health care workers (HCW) are presumably exposed to a higher risk of infection by SARS-CoV-2 and could possibly represent a source of transmission to susceptible patients. Thus, characterization of SARS-CoV-2 infection among HCW is necessary to better understand the determinants of viral transmission and properly implement strategies to prevent dissemination and protect HCW and vulnerable patients. The aim of this study was to estimate the seroprevalence of antibodies against SARS-CoV-2 in a Portuguese tertiary hospital, in the period of July 2020 to March 2021, before the generalized use of the SARS-CoV-2 vaccine, characterize its evolution over time, and identify risk factors associated with seroconversion. Methods: HCW were approached to collect serum samples for qualitative SARS-CoV-2 antibody testing and completion of an online survey capturing demographics, previous symptoms, and details of health care and community exposure. Odds ratio with bivariable and multivariable logistic regression was used to assess characteristics associated with seroprevalence. Results: One thousand HCW were included for analysis. Two hundred nineteen HCW (22%) were seropositive for immunoglobulin G against SARS-CoV-2, and 166 (17%) were seropositive for immunoglobulin M, most of whom reported a previous diagnosis of SARS-CoV-2 infection. The risk factors associated with seroconversion included a previous COVID-19 diagnosis, contact with patients, occupational contact with colleagues, and outside contact. However, in a multivariate logistic regression analysis, only a previous diagnosis and outside contact were associated with seroconversion. Seropositivity decreased over time, especially 28 weeks after infection. Conclusion: HCWs have a high seroprevalence for SARS-CoV-2 infection, probably due to a combination of health care and community exposure. Seropositivity decreases over time, but further studies are needed to better understand our adaptive immune response.

Antimicrobial Stewardship on Patients with Neutropenia: A Narrative Review Commissioned by Microorganisms.

The emergence of antibiotic resistance poses a global health threat. High-risk patients such as those with neutropenia are particularly vulnerable to opportunistic infections, sepsis, and multidrug-resistant infections, and clinical outcomes remain the primary concern. Antimicrobial stewardship (AMS) programs should mainly focus on optimizing antibiotic use, decreasing adverse effects, and improving patient outcomes. There is a limited number of published studies assessing the impact of AMS programs on patients with neutropenia, where early appropriate antibiotic choice can be the difference between life and death. This narrative review updates the current advances in strategies of AMS for bacterial infections among high-risk patients with neutropenia. Diagnosis, drug, dose, duration, and de-escalation (5D) are the core variables among AMS strategies. Altered volumes of distribution can make standard dose regimens inadequate, and developing skills towards a personalized approach represents a major advance in therapy. Intensivists should partner antibiotic stewardship programs to improve patient care. Assembling multidisciplinary teams with trained and dedicated professionals for AMS is a priority.

Features of Mpox infection: The analysis of the data submitted to the ID-IRI network.

Background: Mpox is a rare zoonotic disease caused by the Mpox virus. On May 21, 2022, WHO announced the emergence of confirmed Mpox cases in countries outside the endemic areas in Central and West Africa. Methods: This multicentre study was performed through the Infectious Diseases International Research Initiative network. Nineteen collaborating centres in 16 countries participated in the study. Consecutive cases with positive Mpoxv-DNA results by the polymerase chain reaction test were included in the study. Results: The mean age of 647 patients included in the study was 34.5.98.6% of cases were males, 95.3% were homosexual-bisexual, and 92.2% had a history of sexual contact. History of smallpox vaccination was present in 3.4% of cases. The median incubation period was 7.0 days. The most common symptoms and signs were rashes in 99.5%, lymphadenopathy in 65.1%, and fever in 54.9%. HIV infection was present in 93.8% of cases, and 17.8% were followed up in the hospital for further treatment. In the two weeks before the rash, prodromal symptoms occurred in 52.8% of cases. The incubation period was 3.5 days shorter in HIV-infected Mpox cases with CD4 count <200/µL, we disclosed the presence of lymphadenopathy, a characteristic finding for Mpox, accompanied the disease to a lesser extent in cases with smallpox vaccination. Conclusions: Mpox disseminates globally, not just in the endemic areas. Knowledge of clinical features, disease transmission kinetics, and rapid and effective implementation of public health measures are paramount, as reflected by our findings in this study.

Corynebacterium striatum cardiac device-related endocarditis: A case report.

Corynebacterium striatum is an emerging Gram-positive bacillus associated with invasive infection in both immunocompetent and immunocompromised patients, especially associated with medical devices. Its ability to form biofilms has been demonstrated and it has been occasionally associated with cardiac device-related infective endocarditis with few cases described in literature. We report a case of C. striatum cardiac device-related infective endocarditis of complex management.

Dynamics of a Dual SARS-CoV-2 Lineage Co-Infection on a Prolonged Viral Shedding COVID-19 Case: Insights into Clinical Severity and Disease Duration.

A few molecularly proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding coronavirus disease 2019 (COVID-19) case in a 17-year-old Portuguese female. She had two hospitalizations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days. The viral genome was sequenced in seven serial samples and in the diagnostic sample from her infected mother. A human genome-wide array (>900 K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples. The patient had co-infection by two SARS-CoV-2 lineages, which were affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with the patient's mother), but nine days later, the 20B lineage had 3% frequency, and two months later, the 20B lineage had 100% frequency. The 900 K profiles confirmed the identity of the patient in the serial samples, and they allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort. The early-on dynamic co-infection may have contributed to the severity of COVID-19 in this otherwise healthy young patient, and to her prolonged SARS-CoV-2 shedding profile.

Prospective study of blood viral load of Epstein-Barr virus, herpes virus type 6 and human parvovirus B19 in Crohn's disease: Does therapy matter?

BACKGROUND: The interplay between inflammatory bowel disease (IBD) and DNA viruses, such as Epstein-Barr (EBV), human parvovirus B19 (HPVB19) and human herpes type 6 (HHV6) is scarcely studied. The main aim of this prospective study is to screen for EBV, HSV6, and HPVB19 DNA viremia in adult patients with stable Crohn's disease (CD), correlating the results with IBD treatment. METHODS: From July 2015 - March 2017, 100 patients were enrolled and divided in four groups of 25 participants each, according to in course treatment. Blood collections were performed every 5 months in all patients. Antibodies for EBV and HPVB19 were screened and repeated if negative. Blood EBV DNA, HPVB19 DNA, and HHV6 DNA were quantified by quantitative real-time Polymerase Chain Reaction. RESULTS: Patients had evidence of EBV (100 %) and HPVB19 (70 %) past infection. Across the study timeline, EBV-DNA, HPVB19-DNA, and HHV6-DNA were detected in the blood of 25, 11, and 7 patients, respectively. Viremia was detected only once in 72 %, 73 %, and 86 % of the patients in the studied period, for EBV, HPVB19, and HHV6, respectively. We did not find significant differences between treatment groups, independently of the viral cut-off for the three viruses. CONCLUSIONS: The detection of EBV, HPVB19, and HHV6 viremia, in stable CD patients, was not impacted by biological/immunosuppressant therapy. Although attractive as a non-invasive technique, this approach did not prove to be useful in stable patients. More and larger studies are needed to address the relevance of these viruses on IBD course, in stable patients and during exacerbations.

Preclinical pharmacological evaluation of the fatty acid amide hydrolase inhibitor BIA 10-2474.

BACKGROUND AND PURPOSE: In 2016, one person died and four others had mild-to-severe neurological symptoms during a phase I trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474. EXPERIMENTAL APPROACH: Pharmacodynamic and pharmacokinetic studies were performed with BIA 10-2474, PF-04457845 and JNJ-42165279 using mice, rats and human FAAH expressed in COS cells. Selectivity was evaluated by activity-based protein profiling (APBB) in rats. BIA 10-2474 effect in stroke-prone spontaneously hypertensive rats (SHRSP) was investigated. KEY RESULTS: BIA 10-2474 was 10-fold less potent than PF-04457845 in inhibiting human FAAH in situ but inhibited mouse brain and liver FAAH with ED50 values of 13.5 and 6.2 µg·kg-1 , respectively. Plasma and brain BIA 10-2474 levels were consistent with in situ potency and neither BIA 10-2474 nor its metabolites accumulated following repeat administration. FAAH and α/ß-hydrolase domain containing 6 were the primary targets of BIA 10-2474 and, at higher exposure levels, ABHD11, PNPLA6, PLA2G15, PLA2G6 and androgen-induced protein 1. At 100 mg·kg-1 for 28 days, the level of several lipid species containing arachidonic acid increased. Daily treatment of SHRSP with BIA 10-2474 did not affect mortality rate or increased the incidence of haemorrhage or oedema in surviving animals. CONCLUSIONS AND IMPLICATIONS: BIA 10-2474 potently inhibits FAAH in vivo, similarly to PF-04457845 and interacts with a number of lipid processing enzymes, some previously identified in human cells as off-targets particularly at high levels of exposure. These interactions occurred at doses used in toxicology studies, but the implication of these off-targets in the clinical trial accident remains unclear.

Severe influenza: overview in critically ill patients.

PURPOSE OF REVIEW: Overview of influenza infection, focusing on outcome and complications in critically ill patients. We also discuss relevant elements in immunopathogenesis and their role as predictors of severity. RECENT FINDINGS: Pandemic influenza A (H1N1) virus circulates seasonally and remains the predominant subtype among intensive care patients. Mortality in acute respiratory failure (ARF) is around 20%, independent of influenza subtypes. During severe infection, the imbalance between pro-inflammatory and anti-inflammatory molecules, such as Th1 and Th17 cytokines, is associated with complicated infections and mortality. Primary viral pneumonia presents in more than 70% of ICU influenza patients and more than 50% develop acute respiratory distress syndrome. Bacterial secondary infection occurs in 20% of severe cases and Streptococcus pneumoniae and Staphylococcus aureus remain the prevalent pathogens. Myocarditis and late-onset cardiovascular complications are associated with mortality. Antiviral therapy within 48 h after onset, avoidance of corticosteroids and rescue therapies for ARF or myocarditis, such as extracorporeal membrane oxygenation, improve survival. SUMMARY: The present review summarizes current knowledge on pathogenesis and clinical manifestations of severe influenza. Immunological dysfunction during viral infection correlates with severity and mortality among ICU patients. A theranostics strategy should be implemented to improve outcomes.

STC1 and PTHrP Modify Carbohydrate and Lipid Metabolism in Liver of a Teleost Fish.

Stanniocalcin 1 (STC1) and parathyroid hormone-related protein (PTHrP) are calciotropic hormones in vertebrates. Here, a recently hypothesized metabolic role for these hormones is tested on European sea bass treated with: (i) teleost PTHrP(1-34), (ii) PTHrP(1-34) and anti-STC1 serum (pro-PTHrP groups), (iii) a PTHrP antagonist PTHrP(7-34) or (iv) PTHrP(7-34) and STC1 (pro-STC1 groups). Livers were analysed using untargeted metabolic profiling based on proton nuclear magnetic resonance (1H-NMR) spectroscopy. Concentrations of branched-chain amino acid (BCAA), alanine, glutamine and glutamate increased in pro-STC1 groups suggesting their mobilization from the muscle to the liver for degradation and gluconeogenesis from alanine and glutamine. In addition, only STC1 treatment decreased the concentrations of succinate, fumarate and acetate, indicating slowing of the citric acid cycle. In the pro-PTHrP groups the concentrations of glucose, erythritol and lactate decreased, indicative of gluconeogenesis from lactate. Taurine, trimethylamine, trimethylamine N-oxide and carnitine changed in opposite directions in the pro-STC1 versus the pro-PTHrP groups, suggesting opposite effects, with STC1 stimulating lipogenesis and PTHrP activating lipolysis/ß-oxidation of fatty acids. These findings suggest a role for STC1 and PTHrP related to strategic energy mechanisms that involve the production of glucose and safeguard of liver glycogen reserves for stressful situations.

Mononeuritis multiplex: an uncommon neurological manifestation of cytomegalovirus reactivation in an HIV-infected patient.

BACKGROUND: Cytomegalovirus (CMV) reactivation with neurological involvement in patients with acquired immunodeficiency syndrome (AIDS) is increasingly rare since the introduction of antiretroviral therapy (ART). Manifestations include encephalitis, myelitis, polyradiculopathy and, less commonly, mononeuritis multiplex (MNM). We report a case of disseminated CMV disease with gastrointestinal and peripheral and central nervous system involvement in a patient with AIDS, manifesting primarily as MNM. CASE PRESENTATION: A 31-year old woman with AIDS presented with a clinical picture of MNM. Electromyography confirmed the clinical findings. CMV DNA was detected in cerebrospinal fluid (CSF) and blood. Gastrointestinal involvement was histologically documented. HIV RNA was also detected in CSF and brain MRI was consistent with HIV encephalopathy. A diagnosis of disseminated CMV disease (with esophagitis, colitis, encephalitis and MNM) and HIV encephalopathy was made. Treatment consisted of ganciclovir and foscarnet, followed by maintenance therapy with valganciclovir. Evolution was favorable and valganciclovir was stopped after sustained immune recovery following ART initiation. CONCLUSION: We discuss the diagnostic approach to CMV neurological disease, with a focus on MNM and CMV encephalitis. Combination therapy with ganciclovir and foscarnet should be considered for all forms of neurological involvement, although available data are scarce. Since there is significant overlap between CMV encephalitis and HIV encephalopathy, ART drugs with higher CSF penetration may have to be considered. ART and immune recovery are essential to improve outcomes.

Candidemia in the patient with malignancy.

Invasive fungal infections are a common life-threatening disease and a major cause of morbidity, particularly in patients with malignancies, and Candida spp. is the most common isolated fungi in bloodstream. Candidemia is the focus of this review, which covers an approach to diagnosis and treatment, with an emphasis on patients with malignancies. Acute leukemia, lymphoma, or myelodysplastic syndrome are the most common hematological malignancies associated with candidemia, while among solid tumors, gastrointestinal cancer has the majority of fungemia cases. Epidemiologic trends show there is a discrepancy between malignancies, where there is an important prevalence of non-albicans Candida in hematological malignancy patients. Diagnosis is challenging, and a high index of suspicion is required to select at-risk patients for early empiric therapy with the goal of reducing mortality. There is an increased effort to improve understanding of individualized approaches to the patient based on precision medicine and to improve diagnosis in the future. The basis of treatment is prompt therapy with echinocandins and target therapy based on susceptibility and minimum inhibitory concentrations (MICs).

Evolution of the glucagon-like system across fish.

In fishes, including the jawless lampreys, the most ancient lineage of extant vertebrates, plasma glucose levels are highly variable and regulation is more relaxed than in mammals. The regulation of glucose and lipid in fishes in common with mammals involves members of the glucagon (GCG)-like family of gastrointestinal peptides. In mammals, four peptides GCG, glucagon-like peptide 1 and 2 (GLP1 and GLP2) and glucose-dependent insulinotropic peptide (GIP) that activate four specific receptors exist. However, in lamprey and other fishes the glucagon-like family evolved differently and they retained additional gene family members (glucagon-related peptide, gcrp and its receptor, gcrpr) that are absent from mammals. In the present study, we analysed the evolution of the glucagon-like system in fish and characterized gene expression of the family members in the European sea bass (Dicentrarchus labrax) a teleost fish. Phylogenetic analysis revealed that multiple receptors and peptides of the glucagon-like family emerged early during the vertebrate radiation and evolved via lineage specific events. Synteny analysis suggested that family member gene loss is likely to be the result of a single gene deletion event. Lamprey was the only fish where a putative glp1r persisted and the presence of the receptor gene in the genomes of the elephant shark and coelacanth remains unresolved. In the coelacanth and elephant shark, unique proglucagon genes were acquired which in the former only encoded Gcg and Glp2 and in the latter, shared a similar structure to the teleost proglucagon gene but possessed an extra exon coding for Glp-like peptide that was most similar to Glp2. The variable tissue distribution of the gene transcripts encoding the ligands and receptors of the glucagon-like system in an advanced teleost, the European sea bass, suggested that, as occurs in mammals, they have acquired distinct functions. Statistically significant (p < .05) down-regulation of teleost proglucagon a in sea bass with modified plasma glucose levels confirmed the link between these peptides and metabolism. The tissue distribution of members of the glucagon-like system in sea bass and human suggests that evolution of the brain-gut-peptide regulatory loop diverged between teleosts and mammals despite the overall conservation and similarity of glucagon-like family members.

A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study.

BACKGROUND: Malnutrition and malaria frequently coexist in sub-Saharan African countries. Studies on efficacy of antimalarial treatments usually follow the WHO standardized protocol in which severely malnourished children are systematically excluded. Few studies have assessed the efficacy of chloroquine, sulfadoxine-pyrimethamine and quinine in severe acute malnourished children. Overall, efficacy of these treatments appeared to be reduced, attributed to lower immunity and for some antimalarials altered pharmacokinetic profiles and lower drug concentrations. However, similar research on the efficacy and pharmacokinetic profiles of artemisinin-combination therapies (ACTs) and especially artemether-lumefantrine in malnourished children is currently lacking. The main objective of this study is to assess whether artemether-lumefantrine is less efficacious in children suffering from severe acute malnutrition (SAM) compared to non-SAM children, and if so, to what extent this can be attributed to a sub-optimal pharmacokinetic profile. METHODS/DESIGN: In two sites, Ouelessebougou, Mali and Maradi, Niger, children with uncomplicated microscopically-confirmed P. falciparum malaria aged between 6 and 59 months will be enrolled. Two non-SAM children will be enrolled after the enrolment of each SAM case. Children with severe manifestations of malaria or complications of acute malnutrition needing intensive treatment will be excluded. Treatment intakes will be supervised and children will be followed-up for 42 days, according to WHO guidance for surveillance of antimalarial drug efficacy. Polymerase Chain Reaction genotyping will be used to distinguish recrudescence from re-infection. SAM children will also benefit from the national nutritional rehabilitation program. Outcomes will be compared between the SAM and non-SAM populations. The primary outcome will be adequate clinical and parasitological response at day 28 after PCR correction, estimated by Kaplan-Meier analysis. To assess the pharmacokinetic profile of lumefantrine, a sparse sampling approach will be used with randomized allocation of sampling times (5 per child). A total of 180 SAM children and 360 non-SAM children will be recruited during the 2013 and 2014 malaria seasons. DISCUSSION: This study will provide important information that is currently lacking on the effect of SAM on therapeutic efficacy and pharmacokinetic profile of artemether-lumefantrine. If it shows lower therapeutic efficacy and decreased lumefantrine concentrations, it would inform dose optimization studies in SAM children. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958905.

Comparative evaluation of 11 commercialized rapid diagnostic tests for detecting Trypanosoma cruzi antibodies in serum banks in areas of endemicity and nonendemicity.

Chagas disease is one of the main public health issues in Latin America. Increasingly during the past few decades, Trypanosoma cruzi infection has been detected in North America, Europe, and the Western Pacific, mainly as a result of population movement. The limited availability of rapid serological diagnostic tests hinders rapid diagnosis and early treatment in areas of endemicity and nonendemicity. In collaboration with 11 national reference laboratories (NRLs) from different geographical areas, we evaluated the performances of commercialized serological rapid diagnostic tests (RDT) for T. cruzi infection. Eleven commercialized T. cruzi infection RDTs were evaluated on a total of 474 samples extensively tested with at least three different techniques for Chagas disease, maintained at controlled low temperatures, and stored in the serum banks of the 11 NRLs. We measured the sensitivity, specificity, and concordance of each RDT and provided an additional questionnaire to evaluate its ease of use. The selected RDTs in this study were performed under controlled laboratory conditions. Out of the 11 RDTs, we found 8 of them to be useful, with the cassette format favored over the strip. We did not observe significant differences in RDT performances in the different regions. Overall, the performance results were lower than those disclosed by the manufacturers. The results of this evaluation validate the possibility of using RDTs to diagnose Chagas disease, thereby decreasing the time to treatment at a primary health care facility for patients who are willing to be treated. Further studies should be conducted in the laboratory and in the field to confirm these data, expressly to evaluate reproducibility in resource-limited settings, or using whole blood in clinical settings in areas of endemicity and nonendemicity.

Characteristics of the Colombian armed conflict and the mental health of civilians living in active conflict zones.

BACKGROUND: Despite the fact that the Colombian armed conflict has continued for almost five decades there is still very little information on how it affects the mental health of civilians. Although it is well established in post-conflict populations that experience of organised violence has a negative impact on mental health, little research has been done on those living in active conflict zones. Médecins Sans Frontières provides mental health services in areas of active conflict in Colombia and using data from these services we aimed to establish which characteristics of the conflict are most associated with specific symptoms of mental ill health. METHODS: An analysis of clinical data from patients (N = 6,353), 16 years and over, from 2010-2011, who consulted in the Colombian departments (equivalent to states) of Nariño, Cauca, Putumayo and Caquetá. Risk factors were grouped using a hierarchical cluster analysis and the clusters were included with demographic information as predictors in logistic regressions to discern which risk factor clusters best predicted specific symptoms. RESULTS: Three clear risk factor clusters emerged which were interpreted as 'direct conflict related violence', 'personal violence not directly conflict-related' and 'general hardship'. The regression analyses indicated that conflict related violence was more highly related to anxiety-related psychopathology than other risk factor groupings while non-conflict violence was more related to aggression and substance abuse, which was more common in males. Depression and suicide risk were represented equally across risk factor clusters. CONCLUSIONS: As the largest study of its kind in Colombia it demonstrates a clear impact of the conflict on mental health. Among those who consulted with mental health professionals, specific conflict characteristics could predict symptom profiles. However, some of the highest risk outcomes, like depression, suicide risk and aggression, were more related to factors indirectly related to the conflict. This suggests a need to focus on the systemic affects of armed conflict and not solely on direct exposure to fighting.

Evaluation of clinical and immunological markers for predicting virological failure in a HIV/AIDS treatment cohort in Busia, Kenya.

BACKGROUND: In resource-limited settings where viral load (VL) monitoring is scarce or unavailable, clinicians must use immunological and clinical criteria to define HIV virological treatment failure. This study examined the performance of World Health Organization (WHO) clinical and immunological failure criteria in predicting virological failure in HIV patients receiving antiretroviral therapy (ART). METHODS: In a HIV/AIDS program in Busia District Hospital, Kenya, a retrospective, cross-sectional cohort analysis was performed in April 2008 for all adult patients (>18 years old) on ART for ≥12 months, treatment-naive at ART start, attending the clinic at least once in last 6 months, and who had given informed consent. Treatment failure was assessed per WHO clinical (disease stage 3 or 4) and immunological (CD4 cell count) criteria, and compared with virological failure (VL >5,000 copies/mL). RESULTS: Of 926 patients, 123 (13.3%) had clinically defined treatment failure, 53 (5.7%) immunologically defined failure, and 55 (6.0%) virological failure. Sensitivity, specificity, positive predictive value, and negative predictive value of both clinical and immunological criteria (combined) in predicting virological failure were 36.4%, 83.5%, 12.3%, and 95.4%, respectively. CONCLUSIONS: In this analysis, clinical and immunological criteria were found to perform relatively poorly in predicting virological failure of ART. VL monitoring and new algorithms for assessing clinical or immunological treatment failure, as well as improved adherence strategies, are required in ART programs in resource-limited settings.

Urban cholera transmission hotspots and their implications for reactive vaccination: evidence from Bissau city, Guinea bissau.

BACKGROUND: Use of cholera vaccines in response to epidemics (reactive vaccination) may provide an effective supplement to traditional control measures. In Haiti, reactive vaccination was considered but, until recently, rejected in part due to limited global supply of vaccine. Using Bissau City, Guinea-Bissau as a case study, we explore neighborhood-level transmission dynamics to understand if, with limited vaccine and likely delays, reactive vaccination can significantly change the course of a cholera epidemic. METHODS AND FINDINGS: We fit a spatially explicit meta-population model of cholera transmission within Bissau City to data from 7,551 suspected cholera cases from a 2008 epidemic. We estimated the effect reactive vaccination campaigns would have had on the epidemic under different levels of vaccine coverage and campaign start dates. We compared highly focused and diffuse strategies for distributing vaccine throughout the city. We found wide variation in the efficiency of cholera transmission both within and between areas of the city. "Hotspots", where transmission was most efficient, appear to drive the epidemic. In particular one area, Bandim, was a necessary driver of the 2008 epidemic in Bissau City. If vaccine supply were limited but could have been distributed within the first 80 days of the epidemic, targeting vaccination at Bandim would have averted the most cases both within this area and throughout the city. Regardless of the distribution strategy used, timely distribution of vaccine in response to an ongoing cholera epidemic can prevent cases and save lives. CONCLUSIONS: Reactive vaccination can be a useful tool for controlling cholera epidemics, especially in urban areas like Bissau City. Particular neighborhoods may be responsible for driving a city's cholera epidemic; timely and targeted reactive vaccination at such neighborhoods may be the most effective way to prevent cholera cases both within that neighborhood and throughout the city.

Sentinel site community surveillance of mortality and nutritional status in southwestern Central African Republic, 2010.

BACKGROUND: During 2010, a community-based, sentinel site prospective surveillance system measured mortality, acute malnutrition prevalence, and the coverage of a Médecins Sans Frontières (MSF) intervention in four sous-préfectures of Lobaye prefecture in southwestern Central African Republic. We describe this surveillance system and its evaluation. METHODS: Within 24 randomly selected sentinel sites, home visitors performed a census, weekly demographic surveillance of births, deaths, and in- or out-migration, and weekly anthropometry on a sample of children. We evaluated the system through various methods including capture-recapture analysis and repeat census. RESULTS: The system included 18,081 people at baseline. Over 32 weeks, the crude death rate was 1.0 (95% confidence interval [CI]: 0.8-1.2) deaths per 10,000 person-days (35 deaths per 1,000 person-years), with higher values during the rainy season. The under-5 death rate was approximately double. The prevalence of severe acute malnutrition (SAM) was 3.0% (95% CI: 2.3-4.0), almost half featuring kwashiorkor signs. The coverage of SAM treatment was 29.1%. The system detected >90% of deaths, and >90% of death reports appeared valid. However, demographic surveillance yielded discrepancies with the census and an implausible rate of population growth, while the predictive value of SAM classification was around 60%. DISCUSSION: We found evidence of a chronic health crisis in this remote region. MSF's intervention coverage improved progressively. Mortality data appeared valid, but inaccuracies in population denominators and anthropometric measurements were noted. Similar systems could be implemented in other remote settings and acute emergencies, but with certain technical improvements.