Different Lineages of Chikungunya Virus in Equatorial Guinea in 2002 and 2006

Chikungunya virus is a mosquito-borne virus that causes an acute febrile infection and severe arthralgia and is considered a re-emergent pathogen. During a study investigating arboviruses causing febrile infection in infants in Bata, Equatorial Guinea, the genome of this virus was amplified from blood samples during near two rainy seasons (2002–2003). In 2006, this virus was isolated from a traveler returning to Spain from Equatorial Guinea. These results show that chikungunya virus is present in this country and two lineages are circulating. Thus, this virus should be considered in the differential diagnosis of febrile syndromes in inhabitants and in travelers returning from this country.Tropical Africa is the likely site of origin of many of the arboviruses of modern medical importance. However, there is little data about the prevalence of arboviral infections in this region.Equatorial Guinea is located in the equatorial part of Africa between Cameroon and Gabon and is divided into a continental part (area = 26,017 km²) and some islands (area = 2,034 km²). It has a population of approximately 500,000 persons, with a high percentage (45%) less than 15 years of age. This country has an equatorial climate with an annual average temperature of 25°C. The average annual precipitation (> 2,000 mm) is divided into two rainy seasons: from April to May and from October to December.In west and central Africa, data on the circulation of chikungunya virus (CHIKV) are rare. In Cameroon, serologic prevalence assays have shown that the alphaviruses CHIKV and O''nyong nyong virus are the most common arboviral infections.¹ In Gabon, an outbreak of a dengue-like syndrome caused by CHIKV was described in 2006–2007.² The virus was phylogenetically related to strains isolated in 2006 in Cameroon and seen years earlier in the Democratic Republic of Congo, where 50,000 persons were infected.³Chikungunya virus belongs to the family Togaviridae and the genus Alphavirus. It causes an acute infection with an abrupt onset of fever, headache and severe joint pains and is transmitted mainly by Aedes mosquitoes.⁴ In recent years, it has been considered a re-emergent virus and has become a public health problem in countries such as the Democratic Republic of Congo.³ More recently, CHIKV has caused large outbreaks that affected different Indian Ocean territories and continental India.^5,6 This epidemic was the source of an outbreak in Italy caused by an infected traveler from India.⁷In 2002–2003, a project to study the presence of some viruses in Equatorial Guinea was conducted. Samples from febrile children attending the Reference Center for the Control of Endemic Diseases located in Bata (continental region of Equatorial Guinea) were obtained. From June 2002 to January 2003, 720 blood samples were obtained. RNA was preserved in a guanidinium isothiocyanate buffer. Samples were sent to the National Center for Microbiology in Madrid, Spain, for testing. Samples used were not given personal identifiers to comply with bioethics guides.After RNA extraction,⁸ samples were assayed. We used generic primers to potentially detect arboviruses in different polymerase chain reaction (PCR) assays. We searched for arenaviruses,⁹ hantaviruses, and orthobunyaviruses (using in-house methods); no positive results were obtained. Arboviruses belonging to the genera Flavivirus, Phlebovirus, and/or Alphavirus were tested by using a generic multiplex real-time nested PCR in which consensus primers for each of the three genera were mixed.¹⁰ Positive amplification with the generic multiplex method was achieved in eight samples obtained in the rainy seasons when vector activity is high. Sequences of amplified fragments corresponding to 195 basepairs of the non-structural protein 4 gene of alphaviruses identified a homogeneous cluster of CHIKV belonging to the Central–East/South Africa genotype. Chikungunya virus was found in 2002 (three samples in June, one sample in July, and two samples in December) and 2003 (two samples in January). Four of these eight virus-positive samples were also positive for Plasmodium falciparum.To obtain a sequence with more phylogenetic information, primers designed by Powers and others (sense ₁₀₂₄₆ 5′-TTACCCNTTYATGTGGGG-3′₁₀₂₆₂ and antisense ₁₀₇₉₃ 5′-CTTACSGGGTTTGTYGC-3′₁₀₇₇₇),¹¹ were used in combination with primer₁₀₇₁₄ 5′-TRAAGCCAGATGGTGCC-3′₀₆₉₈ to amplify a fragment of a region of the envelope 1 (E1) gene often used for CHIKV phylogenetic analysis. Three of the eight positive samples (probably those with the highest concentration of virus) showed a 469-basepair product whose sequences formed a unique cluster within the Central/East African genotype clade (Figure 1).Open in a separate windowFigure 1.Phylogenetic tree showing the relationships of chikungunya virus (CHIK) strains. A 434-basepair fragment from the envelope 1 gene was analyzed by using the neighbor-joining method, the number of differences model, and bootstrap percentage corresponding to 1,000 replicates with the MEGA 4 software. O''nyong nyong virus (ONNV) was used as an outgroup. Accession number, name of the strain, and place and year of isolation are indicated. Strains sequenced in this paper are shown in bold. Bootstrap values > 80 are shown.In Spain, CHIKV was considered in the differential diagnosis of a febrile syndrome in travelers returning from Equatorial Guinea. In 2006, one of three such travelers returning from this area was diagnosed in Spain as being infected with CHIKV on the basis of a positive PCR result, which showed amplification of part of the E1 gene.¹² This sequence is similar to others described at the same time from Cameroon and Gabon,^1,2 but is different from sequences obtained in Equatorial Guinea in 2002. There is evidence of endemic circulation of a genetically stable monophyletic CHIKV population during 2000–2007 in west central Africa.²Our results suggest that a paraphyletic population of CHIKV was circulating in Equatorial Guinea in 2002. Our results indicate that CHIKV is likely endemic in Equatorial Guinea, and suggest that either two (or more) CHIKV populations were co-circulating in Equatorial Guinea or the western Central African lineage has replaced the lineage detected during 2002–2003. Our data clearly identified three genotypes but cannot be used to unequivocally demonstrate the endemicity of CHIKV in Equatorial Guinea. To conduct a robust phylogenetic analysis, complete sequences of viruses belonging to each group are needed. Therefore, studies of CHIKV in patients infected in Equatorial Guinea are ongoing.     

Mucinous cystadenoma of the retroperitoneum, laparoscopy or an open approach? Two case reports and review of the literature

Big cystic lesions of the retroperitoneum are rare entities. Most of the cases involved females of reproductive age and were related to ovarian structures. The recommended treatment is surgery, and more than 90% of the reported cases were resected in an open midline abdominal incision. We present two patients who were referred to our clinic due to abdominal mass that was causing vague abdominal pain. Homogenic retroperitoneal cystic mass was demonstrated on computerized tomography (CT). One was resected by laparoscopy and the other by laparotomy, both revealed a mucinous cystadenoma of the retroperitoneum. A review of the literature is also presented.     

Measuring the quality of life of the elderly in health promotion intervention clinical trials.

The Multicenter Trials of Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) is a series of clinical trials of biomedical, behavioral, and environmental interventions to reduce the risks of frailty and injury among the elderly. Reliable assessment of the quality of life reported by the subjects is a central issue in evaluating the interventions. An intervention may have a significant impact on an elderly person's sense of well-being, even though significant improvement is not observed in selected physical outcome measures. Elderly persons' compliance with particular intervention regimens may be influenced by the quality of life effects that they perceive in relation to the intervention. The researchers review the definition and measurement of quality of life in the trials, with particular attention to issues in determining common measures used at all study locations. Practical considerations in the selection and use of quality of life measures in both community and institutional populations are addressed. Topics discussed include the interrelation of aging, functional capacities, and quality of life; the multi-dimensionality of quality of life in relation to differential intervention effects; and age-related issues in the collection of quality of life data. Preliminary observations are reviewed, and potential contributions of FICSIT to intervention-sensitive quality of life assessments among the elderly are noted.     

Drug-induced myoclonus: a French pharmacovigilance database study

Various drugs have been reported to induce myoclonus. However, this adverse event is not well known because of the difficult diagnosis and the lack of pharmaco-epidemiological or controlled studies. As far as we know, there are only case reports. In the literature, antiparkinsonian medications, antipsychotics, antidepressants, anesthetics, opiates and anti-infectious drugs have been reported in the occurrence of myoclonus. In a French pharmacovigilance database study, only 423 reports (0.2%) involved drug-induced myoclonus. The median age of patients was 55 years and 10% of these patients had a concomitant neurological disease. Only 16% of these reports had a strong imputability score (likely). The most frequently involved drugs were anti-infectious (15%), antidepressants (15%), anxiolytics (14%), and opiates agents (12%). Fifty-six percent of these reports were classified as serious adverse event. Concerning outcome, most patients (84%) recovered without sequels.     

Management of ectopic pregnancy

Risk factors for ectopic pregnancy include previous ectopic pregnancy, current intrauterine device use, prior fallopian tube surgery, previous pelvic inflammatory disease and a prior history of infertility. Abdominal pain is the most common symptom, followed by amenorrhea or vaginal bleeding, nausea, vomiting, syncope and dizziness. Referred shoulder pain following the onset of abdominal pain is characteristic of intraperitoneal bleeding and, in the appropriate clinical setting, strongly suggests a ruptured ectopic pregnancy. A coordinated evaluation includes measurement of serum human chorionic gonadotropin concentration and transabdominal or, preferably, transvaginal ultrasonography. Treatment is primarily by one of a variety of surgical techniques. Medical therapy with methotrexate or other drugs is currently under investigation.     

The Influence of Organizational Culture on School‐Based Obesity Prevention Interventions: A Systematic Review of the Literature

BACKGROUND

Although the influence of organizational culture has been examined on a variety of student outcomes, few studies consider the influence that culture may have on school‐based obesity prevention interventions. We present a systematic review of the literature to examine how elements of organizational culture may affect the adoption, implementation, and sustainability of school‐based obesity prevention interventions.

METHODS

Fourteen studies examining the impact of organizational‐level characteristics on school‐based obesity prevention interventions were identified through the online databases EBSCO (CINAHL, ERIC, Agricola), Web of Science, Medline (PubMed), and Scopus.

RESULTS

Five themes were identified as elements of organizational culture that influence the adoption, implementation, and sustainability of school‐based obesity prevention interventions: organizational response to limited resources, value placed on staff training and professional development, internal support, organizational values, and school climate.

CONCLUSIONS

Organizational culture can greatly influence the success of school‐based obesity interventions. The collection of data related to organizational‐level factors may be used to identify strategies for creating and sustaining a supportive environment for obesity prevention interventions in the school setting.

     

Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial

OBJECTIVE: RANKL is essential for osteoclast development, activation, and survival. Denosumab is a fully human monoclonal IgG2 antibody that binds RANKL, inhibiting its activity. The aim of this multicenter, randomized, double-blind, placebo-controlled, phase II study was to evaluate the effects of denosumab on structural damage in patients with rheumatoid arthritis (RA) receiving methotrexate treatment. METHODS: RA patients received subcutaneous placebo (n = 75), denosumab 60 mg (n = 71), or denosumab 180 mg (n = 72) injections every 6 months for 12 months. The primary end point was the change from baseline in the magnetic resonance imaging (MRI) erosion score at 6 months. RESULTS: At 6 months, the increase in the MRI erosion score from baseline was lower in the 60-mg denosumab group (mean change 0.13; P = 0.118) and significantly lower in the 180-mg denosumab group (mean change 0.06; P = 0.007) than in the placebo group (mean change 1.75). A significant difference in the modified Sharp erosion score was observed as early as 6 months in the 180-mg denosumab group (P = 0.019) as compared with placebo, and at 12 months, both the 60-mg (P = 0.012) and the 180-mg (P = 0.007) denosumab groups were significantly different from the placebo group. Denosumab caused sustained suppression of markers of bone turnover. There was no evidence of an effect of denosumab on joint space narrowing or on measures of RA disease activity. Rates of adverse events were comparable between the denosumab and placebo groups. CONCLUSION: Addition of twice-yearly injections of denosumab to ongoing methotrexate treatment inhibited structural damage in patients with RA for up to 12 months, with no increase in the rates of adverse events as compared with placebo.