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Summary: Background: Colposcopy, currently included in WHO recommendations as an option to triage human papillomavirus (HPV)-positive women, remains as the reference standard to guide both biopsy for confirmation of cervical precancer and cancer and treatment approaches. We aim to evaluate the performance of colposcopy to detect cervical precancer and cancer for triage in HPV-positive women. Methods: This cross-sectional, multicentric screening study was conducted at 12 centres (including primary and secondary care centres, hospitals, laboratories, and universities) in Latin America (Argentina, Bolivia, Colombia, Costa Rica, Honduras, Mexico, Paraguay, Peru, and Uruguay). Eligible women were aged 30–64 years, sexually active, did not have a history of cervical cancer or treatment for cervical precancer or a hysterectomy, and were not planning to move outside of the study area. Women were screened with HPV DNA testing and cytology. HPV-positive women were referred to colposcopy using a standardised protocol, including biopsy collection of observed lesions, endocervical sampling for transformation zone (TZ) type 3, and treatment as needed. Women with initial normal colposcopy or no high-grade cervical lesions on histology (less than cervical intraepithelial neoplasia [CIN] grade 2) were recalled after 18 months for another HPV test to complete disease ascertainment; HPV-positive women were referred for a second colposcopy with biopsy and treatment as needed. Diagnostic accuracy of colposcopy was assessed by considering a positive test result when the colposcopic impression at the initial colposcopy was positive minor, positive major, or suspected cancer, and was considered negative otherwise. The main study outcome was histologically confirmed CIN3+ (defined as grade 3 or worse) detected at the initial visit or 18-month visit. Findings: Between Dec 12, 2012, and Dec 3, 2021, 42 502 women were recruited, and 5985 (14·1%) tested positive for HPV. 4499 participants with complete disease ascertainment and follow-up were included in the analysis, with a median age of 40·6 years (IQR 34·7–49·9). CIN3+ was detected in 669 (14·9%) of 4499 women at the initial visit or 18-month visit (3530 [78·5%] negative or CIN1, 300 [6·7%] CIN2, 616 [13·7%] CIN3, and 53 [1·2%] cancers). Sensitivity was 91·2% (95% CI 88·9–93·2) for CIN3+, whereas specificity was 50·1% (48·5–51·8) for less than CIN2 and 47·1% (45·5–48·7) for less than CIN3. Sensitivity for CIN3+ significantly decreased in older women (93·5% [95% CI 91·3–95·3] in those aged 30–49 years vs 77·6% [68·6–85·0] in those aged 50–65 years; p

Objective: The aim of this research was to evaluate the efficacy and safety of Er:YAG lasers to improve signs and symptoms of vulvar lichen sclerosus. Methods: The study population consisted of 28 women with symptomatic vulvar lichen sclerosus. Three nonablative, thermal-only Er:YAG laser treatment sessions (7 J/cm2, 2 Hz, 7 mm spot) were performed at 4-week intervals. Each patient was asked about the presence of symptoms, such as itching, pain, and coital pain. Clinical diagnosis was established on the basis of the presence of lesions such as hypopigmentation, ecchymosis, hyperkeratosis, excoriations, or fissures. The affected areas were divided by zones (clitoris, introitus, labia minora, labia majora, perineum, labial fusion, and effacement) and were visually evaluated. Based on the presence of symptoms, lesions, and affected zones, a scale with a maximum of 14 scores was established for use before and after treatment. The impact of lichen sclerosus on patients' lives before and after treatment was evaluated with an 11-point visual analogue scale, and treatment discomfort was assessed at each session. Results: After analysis of each scoring component, individual statistically significant reductions were observed in itching, pain, ecchymosis, excoriations, and hypopigmentation. Conclusion: The Er:YAG laser is a safe, well tolerated, and effective method for the adjuvant treatment of vulvar lichen sclerosus. Three sessions with monthly intervals using the indicated parameters can quantifiably reduce the impact of lichen sclerosus on patients' lives. Keywords: erbium laser, vulvar lichen sclerosus

Objective: To characterize the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically guided multivariable model. Patients and Methods: The Spanish Group of Autoimmune Diseases HLH Study Group, formed in 2013, is aimed at collecting adult patients with HLH diagnosed in internal medicine departments between January 3, 2013, and October 28, 2017. Results: The cohort consisted of 151 patients (91 men; mean age, 51.4 years). After a mean follow-up of 17 months (range, 1-142 months), 80 patients died. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia (P

Background: Since 2006, many countries have implemented publicly funded human papillomavirus (HPV) immunisation programmes. However, global estimates of the extent and impact of vaccine coverage are still unavailable. We aimed to quantify worldwide cumulative coverage of publicly funded HPV immunisation programmes up to 2014, and the potential impact on future cervical cancer cases and deaths. Methods: Between Nov 1 and Dec 22, 2014, we systematically reviewed PubMed, Scopus, and official websites to identify HPV immunisation programmes worldwide, and retrieved age-specific HPV vaccination coverage rates up to October, 2014. To estimate the coverage and number of vaccinated women, retrieved coverage rates were converted into birth-cohort-specific rates, with an imputation algorithm to impute missing data, and applied to global population estimates and cervical cancer projections by country and income level. Findings: From June, 2006, to October, 2014, 64 countries nationally, four countries subnationally, and 12 overseas territories had implemented HPV immunisation programmes. An estimated 118 million women had been targeted through these programmes, but only 1% were from low-income or lower-middle-income countries. 47 million women (95% CI 39–55 million) received the full course of vaccine, representing a total population coverage of 1·4% (95% CI 1·1–1·6), and 59 million women (48–71 million) had received at least one dose, representing a total population coverage of 1·7% (1·4–2·1). In more developed regions, 33·6% (95% CI 25·9–41·7) of females aged 10–20 years received the full course of vaccine, compared with only 2·7% (1·8–3·6) of females in less developed regions. The impact of the vaccine will be higher in upper-middle-income countries (178 192 averted cases by age 75 years) than in high-income countries (165 033 averted cases), despite the lower number of vaccinated women (13·3 million vs 32·2 million). Interpretation: Many women from high-income and upper-middle-income countries have been vaccinated against HPV. However, populations with the highest incidence and mortality of disease remain largely unprotected. Rapid roll-out of the vaccine in low-income and middle-income countries might be the only feasible way to narrow present inequalities in cervical cancer burden and prevention. Funding: PATH, Instituto de Salud Carlos III, and Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR).

Mitochondrial DNA mutations have been associated with different illnesses in humans, such as Kearns-Sayre syndrome (KSS), which is related to deletions of different sizes and positions among patients. Here, we report a Mexican patient with typical features of KSS containing a novel deletion of 7629 bp in size with 85% heteroplasmy, which has not been previously reported. Sequence analysis revealed 3-bp perfect short direct repeats flanking the deletion region, in addition to 7-bp imperfect direct repeats within 9-10 bp. Furthermore, sequencing, alignment and phylogenetic analysis of the hypervariable region revealed that the patient may belong to a founder Native American haplogroup C4c.

A total of 1,220 subjects from Equatorial Guinea living in Spain (median age = 41 years; 453 male and 767 female) was examined for antibodies to human immunodeficiency virus (HIV) and Hepatitis B (HBV), C (HCV), and D (HDV) viruses. Extracted RNA and DNA from the positive samples were used to quantify viral load. The prevalence of HIV antibodies, HCV RNA, and HBV surface antigen (HBsAg) was 10.8% (N = 132), 11.6% (N = 141), and 7.9% (N = 96), respectively. The most prevalent HIV variant was CRF02_AG (38.5%; N = 40). HCV genotype 4 (60%; N = 36) and HBV genotype A3 (32%; N = 8) were the hepatitis variants most frequently found. Superinfection with HDV was seen in 20.9% (N = 24) of HBsAg carriers. A control group of 276 immigrants from other sub-Saharan countries showed similar rates of HIV and HBsAg, although no HCV cases were found. Immigrants constitute a major source of HIV and hepatitis viruses in Spain; therefore, it is important that control measures are intensified.

Background: Submicroscopic malaria (SMM) can be defined as low-density infections of Plasmodium that are unlikely to be detected by conventional microscopy. Such submicroscopic infections only occasionally cause acute disease, but they are capable of infecting mosquitoes and contributing to transmission. This entity is frequent in endemic countries; however, little is known about imported SMM.The goals of this study were two-fold: a) to know the frequency of imported SMM, and b) to describe epidemiological, laboratorial and clinical features of imported SMM., Methods: A retrospective study based on review of medical records was performed. The study population consisted of patients older than 15 years attended at the Tropical Medicine Unit of Hospital Carlos III, between January 1, 2002 and December 31, 2007. Routinely detection techniques for Plasmodium included Field staining and microscopic examination through thick and thin blood smear. A semi-nested multiplex malaria PCR was used to diagnose or to confirm cases with low parasitaemia., Results: SMM was diagnosed in 104 cases, representing 35.5% of all malaria cases. Mean age (IC95%) was 40.38 years (37.41-43.34), and sex distribution was similar. Most cases were in immigrants, but some cases were found in travellers. Equatorial Guinea was the main country where infection was acquired (81.7%). Symptoms were present only in 28.8% of all SMM cases, mainly asthenia (73.3% of symptomatic patients), fever (60%) and arthromialgias (53.3%). The associated laboratory abnormalities were anaemia (27.9%), leukopaenia (15.4%) and thrombopaenia (15.4%). Co-morbidity was described in 75 cases (72.1%)., Conclusions: Results from this study suggest that imported SMM should be considered in some patients attended at Tropical Medicine Units. Although it is usually asymptomatic, it may be responsible of fever, or laboratory abnormalities in patients coming from endemic areas. The possibility of transmission in SMM has been previously described in endemic zones, and presence of vector in Europe has also been reported. Implementation of molecular tests in all asymptomatic individuals coming from endemic area is not economically feasible. So re-emergence of malaria (Plasmodium vivax) in Europe may be speculated.

Introduction: Up to now, the epidemiological and clinical features of imported malaria in Spain have been described in small series from general hospitals. Almost all diagnosis had been made based on symptomatic patients. The aim of this study has been to determine the epidemiological, clinical and laboratorial characteristics of imported malaria in a Reference Unit for Tropical Diseases., Patients and Methods: We performed a cross-sectional, observational and retrospective study. The series consisted of patients diagnosed of malaria who had been attended at the Hospital Carlos III from January 1, 2002 to December 31, 2007., Results: We identified 484 episodes of malaria, of which 398 cases were included in the analysis. Almost 50% of the patients were natives of endemic areas, while the rest were native-travelers or travelers. Most cases (88-98% according to the group) had not taken malaria chemoprophylaxis correctly when indicated. At the time of diagnosis, 30.4% of patients were asymptomatic and 28.1% of asymptomatic patients had anemia, 19.8% thrombocytopenia, 14% leukopenia, 5% hypocholesterolemia, 5% renal failure and 4.1% hypoglycemia. Low parasitemia was present in 97.5% of asymptomatic individuals compared to 80.5% of the symptomatic patients (P<0.001)., Discussion: Absence of chemoprophylaxis (or poor compliance) is the main reason for malaria in individuals traveling to endemic areas. Malaria must be ruled out in individuals coming from tropical countries with compatible symptoms, and it also should be suspected in certain groups of asymptomatic individuals with abnormal laboratorial parameters., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Introduction: Few data are available in Spain data on human immunodeficiency virus (HIV) patients coinfected with malaria. This study has aimed to determine the epidemiological and clinical characteristics of imported malaria in patients coinfected with HIV., Patients and Methods: A case-series retrospective study was performed using the patient's medical records. The study population consisted on patients diagnosed with malaria attended in our center from january 1, 2002 to december 31, 2007., Results: A total of 484 episodes of malaria, 398 of which were included in this study, were identified. Co-infection with HIV was described in 32 cases. All of them occurred in individuals presumably with some degree of semi-immunity. In the coinfected group, there were 13 cases (40.6%) asymptomatic, whereas this event occurred in 99 cases of patients not coinfected (37.2%) (P=0.707). The greater presence of anemia in co-infected patients (62.5% vs 32.3% in non-coinfected [P=0.001]) stands out., Conclusions: In present study, the clinical presentation forms were similar, regardless of the presence or absence of HIV infection. Although the study population does not reflect all possible scenarios of malaria and HIV coinfection, our results indicate the reality of patients attended in the Autonomous Community of Madrid., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Paracoccidioidomycosis is the most important systemic mycosis in South America. In Europe the disease is very rare and only found in returning travelers. Here we report on a 56-year-old Spanish missionary with respiratory symptoms but no other affected systems. Diagnosis was made based on serology and PCR for Paracoccidioides brasiliensis.

Abstract The diagnosis of HIV-1 is increasing in African-born persons residing in Europe. They present a high prevalence of HIV-1 non-B variant infections and of parasitic infections, both of which are infrequent in Western countries. Immigration favors their presence in nonendemic countries. In this study, all newly HIV-diagnosed individuals at an HIV/AIDS and Tropical Medicine reference center in Madrid from 2005 through 2007 were retrospectively studied. HIV-1 subtyping was performed in gag, pol, and gp41 coding regions by phylogenetic analyses. The presence of other pathogens was also evaluated. Furthermore, all HIV-1-infected Africans were screened for parasitic infections. Newly diagnosed HIV-1 subjects included 90 sub-Saharan Africans and 188 non-Africans (116 Spaniards, 13 other Europeans, and 59 Latin Americans). Significantly higher numbers of HIV-1-infected Africans than non-Africans were females, acquired HIV-1 by heterosexual contact, and presented a more advanced clinical CDC stage and criteria for starting antiretroviral therapy in the first clinical visit. They predominantly carried non-B subtype infections, mainly intersubtype recombinants. Half of HIV-1-infected Africans had parasitic infections. CD4(+) T cell counts were lower among Africans than Europeans at the time of HIV-1 diagnosis. At 12 months of follow-up after starting antiretroviral treatment, a significantly lower proportion of Africans than non-Africans achieved undetectable viremia due to their higher loss to follow-up. However, CD4(+) T cell recovery and virological failure rates were similar. Therefore, the profile of African HIV-1-infected immigrants varies widely with respect to Spanish HIV-infected individuals. More advanced immunodeficiency and the coexistence of parasitic diseases and infections with a large diversity of HIV-1 non-B and recombinant variants are expected.

Initially described in travelers, outbreaks of cyclosporiasis were soon linked to imported food products. An outbreak of cyclosporiasis in Spanish travelers is described. After identification of Cyclospora cayetanensis in stool analyses, a specific questionnaire was completed. Pyrosis was described in 57% of cases (4/7). Peptic symptoms can be a useful clue to indicate the diagnosis of cyclosporiasis in patients with travelers' diarrhea.

Background: Anisakis simplex is a nematode which can parasitize humans, producing anisakiasis and can induce immunoglobulin-(Ig)-E-mediated allergic symptoms. Parasite recombinant proteins, such as the major allergen Ani s 1, may be useful tools to avoid misdiagnosis of A simplex allergy due to cross-reactivity when whole parasite extracts are used., Objective: To obtain Ani s 1 allergen as a recombinant protein with IgE-binding properties similar to its natural counterpart., Methods: Ani s 1-encoding cDNA was amplified by polymerase chain reaction and cloned. The allergen was expressed in Escherichia coli as a nonfusion protein. Natural and recombinant Ani s 1 were investigated by means of Western blotting, enzyme allergosorbent test, enzyme-linked immunosorbent assay (ELISA), and ELISA inhibition using sera from 53 patients with A simplex allergy., Results: Residues of the amino acid sequence of the encoded protein were 99.4% identical to the reported one. Purified rAni s 1 was obtained with a yield of 2 mg/L of culture while the yield of the natural counterpart was only 50 micro/g of larvae. rAni s 1 reactivity was not significantly different from that of the natural allergen; the correlation was excellent (p = 0.92, P < .001). ELISA-inhibition experiments showed that the dose-response inhibition curve obtained with rAni s 1 overlapped with that of nAni s 1. In an enzyme allergosorbent analysis, 86.8% of the A simplex-allergic patient sera reacted to rAni s 1., Conclusion: Recombinant Ani s 1 is immunochemically equivalent to its natural counterpart and therefore might be useful for the in vitro diagnosis of anisakiasis and A simplex-mediated allergy.

The incidence or severity of certain vaccine-preventable diseases is higher in HIV-infected individuals. However, immune responses to vaccination may be diminished, particularly in those with severe immunosuppression. Higher doses of vaccine, more frequent boosters, or revaccination after antiretroviral therapy-induced immune reconstitution are strategies to be considered for patients in certain circumstances. In addition, some vaccines may be harmful when given to severely immunocompromised patients. The challenge for healthcare providers is assessing the safety and effectiveness of vaccines for HIV-infected patients, especially when information on vaccines has not been fully characterized in the HIV-setting. This review presents state-of-the-art knowledge about immunizations for HIV-adults. The efficacy and safety of current vaccines, their current indications in HIV-infected adults, and the strategies aimed to enhance their results are discussed.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by mutations in the thymidine phosphorylase gene (ECGF1). We present the first detailed report of a Brazilian MNGIE patient, harboring a novel ECGF1 homozygous mutation (C4202A, leading to a premature stop codon, S471X). Multiple deletions and the T5814C change were found in mitochondrial DNA. Together with gastrointestinal symptoms, endocrine involvement and memory dysfunction, not reported in MNGIE to date, were the most preeminent features.

Malaria and HIV infection are both prevalent in the areas of the world where these diseases have the largest burden. Both diseases interact with one another and this interaction is especially important in areas with non-continuous malaria transmission, in pregnant women, and in patients with more severe immunodeficiency. Malaria has been implicated in transitory higher viral load and in low CD4 counts, so it could have an influence on higher transmission rates of HIV and perhaps in the course of HIV infection. Infection with HIV has been shown to cause more clinical malaria and higher parasitemia in patients living in perennial transmission areas, and higher rates of severe malaria episodes and mortality in areas where malaria is transmitted with seasonal frequency. The HIV-infected patients have also higher rates of malaria treatment failures. Co-trimoxazole prophylaxis has been shown to be effective in the prevention of some opportunistic infections in HIV-infected patients, but also in prevention of malaria episodes. Antiretroviral protease inhibitors demonstrate antimalarial effects that could have important clinical and therapeutic implications. For all of these reasons, HIV and malaria should be considered together as part of healthcare programs for both diseases in countries where their co-presence favors an interaction with important clinical consequences.

Introduction: Mitochondrial encephalopathy, lactic acidosis and cerebrovascular accident syndrome (MELAS) is, from the clinical point of view, one of the best studied mitochondrial multisystemic disorders. This disease has mainly been associated to the mitochondrial desoxyribonucleic acid (mtDNA) mutation A3243G located in the tRNALeu(UUR) gene. Although a relation between European haplogroups and the presence of the 3243 mutation has not been described, nothing is known about the presence of this mutation in native American haplogroups., Case Report: A 12 year-old female Mexican patient diagnosed with MELAS is reported. Besides neurological, biochemical and cytological examination, we also analyzed the particular mtDNA mutations related to MELAS and the whole genome was sequenced to determine the mitochondrial haplogroup. The A3243G mutation was detected in the patient and maternal relatives (mother and siblings, all of them asymptomatic). The genotype corresponds to the native American haplogroup B2 and contains two private non-synonymous polymorfisms., Conclusion: All the members of the family studied present different percentage of the A3243G mutation, being the patient who presented the highest value. The mtDNA genotype corresponds to the native American haplogroup B2 and the private polymorphisms do not confer any phenotypic modification in MELAS syndrome.

Aim: The diseases of the oxidative phosphorylation system consist of a group of disorders originated by a deficient synthesis of adenosine triphosphate (ATP). These diseases are increasingly being diagnosed among patients with multisystemic disorders. Mitochondrial deoxyribonucleic acid (mtDNA) mutations are usually maternally inherited, but they also can be sporadic or secondary to nuclear mutations, that are inherited in a Mendelian mode, or due to environmental hazards. In this review we will update, from a genetic point of view, the knowledge on human mitochondrial diseases, remarking the difficulties to study these pathologies., Development: To mirror these difficulties, we will use selected examples of mutations in the mitochondrial genome, and review recent advances on mitochondrial pathology due to mutations in the nuclear genes codifying for mitochondrial proteins that participate in a good performance of the oxidative phosphorylation system., Conclusions: Sequencing of the complete human mtDNA should be part of the basic profile in the study of mitochondrial diseases. Due to the increasing number of nuclear genes involved in the oxidative phosphorylation system performance, their analysis should be based on solid biochemical clues.

Introduction: Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterized by progressive external ophthalmoplegia, pigmentary retinopathy, onset before 20 years, and ragged-red fibers on muscle biopsy. KSS has been associated to mitochondrial DNA (mtDNA) mutations. We report neurological manifestations and mtDNA deletions in KSS., Methods: Six KSS patients underwent neurological examination, biochemical analysis (muscle enzymes, lactate, cerebrospinal fluid analysis), electromicrography, muscle biopsy (Gomori stain, electronic microscopy), electrocardiogram, echocardiography, MRI/CT scan. MtDNA deletions were studied in blood and muscle samples using Southern blotting and long polymerase chain reaction., Results: Four males and two females (mean age: 27.7 years; range: 17-42; mean age at onset: 8.2 years) were studied. Initial symptoms were ptosis and gaze restriction, fatigue, exercise intolerance and proximal limb weakness. Syncope and neurosensory hypoacusia were initial symptoms in two patients. All of them presented a unique deletion in the mitochondrial genome, in heteroplasmy, and their size was in the range of 4,420 and 9,437 basis pairs. Three of these deletions are reported for the first time in this article. Most of the deletions are flanked by small direct repeats elements., Conclusions: Proximal muscle weakness and fatigue appear frequently in KSS patients during follow up. The syndrome in these patients has been caused by mtDNA deletions.

Objectives: To identify the prescription profile for anti-ulcerous and hypolipemic drugs during the three-year period 1994-1996 in the Jerez Primary Care district, and the differences in prescription between the reformed (Health Centres) and the unreformed networks (non-hospital clinics)., Design: Longitudinal, retrospective study, out of a complete sample., Setting: Primary Care., Participants: Total number of general medical consultations., Measurements and Main Results: The first quarter of each year was studied. Dose per 1,000 inhabitants per day (DID) was the indicator. Consumption of anti-ulcer drugs grew from 11.43 DID in 1994 to 15 in 1996 (31.23%). In the reformed network, consumption grew from 10.25 to 13.26 DID (29.37%); and in the non-reformed, from 12.56 to 16.72 DID (33.12%). Hypolipemic use went up from 8 DID in 1994 to 10.32 in 1996 (29%)., Conclusions: Anti-ulcer and hypolipemic drug use increased over the study period. Both consumption and increases were lower in Health Centres. Increase in statin use led to a light decline in fibrate use in the reformed network, but not in non-hospital clinics.