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Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) is a vector of visceral leishmaniasis in the Americas and it might represent a complex of sibling species. Reproductive isolation between closely related species often involves differences in courtship behaviour. cacophony (cac) and period (per) are two Drosophila genes that control features of the "lovesong" males produce during courtship that has been implicated in the sexual isolation between closely related species. We are using gene fragments from L. longipalpis' homologues of these two genes to study the speciation process in this putative species complex.

Abstract Background Lamivudine is an oral nucleoside analogue widely used for the treatment of chronic hepatitis B. The main limitation of lamivudine use is the selection of resistant mutations that increases with time of utilization. Hepatitis B virus (HBV) isolates have been classified into eight genotypes (A to H) with distinct geographical distributions. HBV genotypes may also influence pathogenic properties and therapeutic features. Here, we analyzed the HBV genotype distribution and the nature and frequency of lamivudine resistant mutations among 36 patients submitted to lamivudine treatment for 12 to 84 months. Results Half of the patients were homosexual men. Only 4/36 (11%) patients were HBV DNA negative. As expected for a Brazilian group, genotypes A (24/32 positive individuals, 75%), D (3/32, 9.3%) and F (1/32, 3%) were present. One sample was from genotype C, which is a genotype rarely found in Brazil. Three samples were from genotype G, which had not been previously detected in Brazil. Lamivudine resistance mutations were identified in 20/32 (62%) HBV DNA positive samples. Mean HBV loads of patients with and without lamivudine resistance mutations were not very different (2.7 × 107 and 6.9 × 107 copies/mL, respectively). Fifteen patients showed the L180M/M204V lamivudine resistant double mutation. The triple mutant rt173V/180M/204V, which acts as a vaccine escape mutant, was found in two individuals. The three isolates of genotype G were entirely sequenced. All three showed the double mutation L180M/M204V and displayed a large genetic divergence when compared with other full-length genotype G isolates. Conclusion A high (55%) proportion of patients submitted to long term lamivudine therapy displayed resistant mutations, with elevated viral load. The potential of transmission of such HBV mutants should be monitored. The identification of genotypes C and G, rarely detected in South America, seems to indicate a genotype distribution different to that observed in non treated patients. Disparities in routes of transmission (genotype G seems to be linked to homosexual behavior) and in pathogenic properties (genotype C is very aggressive) among HBV genotypes may explain the presence of rare genotypes in the present work.

The COVID-19 pandemic took a toll on everyone's lives, and patients with rare diseases (RDs) had to pay an even higher price. In this systematic review, we explored the impact of the COVID-19 pandemic on individuals with RDs from a psychological perspective. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we retrieved articles from the Google Scholar, Scopus, and PubMed databases focusing on 'COVID-19,' 'psychology,' and 'rare diseases.' Seventeen primary articles were identified (mainly from continental Europe). The results revealed the psychological effects of the pandemic on rare disease patients, including increased anxiety, stress, and depressive moods. This review also highlighted the increased vulnerability and reduced quality of life of rare disease patients during the pandemic, as well as the importance of telecare and psychological support as critical interventions for improving their well-being. There is an urgent need for multidisciplinary research and stronger healthcare systems to meet the unique challenges of rare disease patients, who represent 3.5-5.9% of the global population.

Background: Household surveys remain important sources of stillbirth data, but omission and misclassification are common. Classifying adverse pregnancy outcomes as stillbirths requires accurate reporting of vital status at birth and gestational age or birthweight for every pregnancy. Further categorisation, e.g. by sex, or timing (intrapartum/antepartum) improves data to understand and prevent stillbirth., Methods: We undertook a cross-sectional population-based survey of women of reproductive age in five health and demographic surveillance system sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda (2017-2018). All women answered a full birth history with pregnancy loss questions (FBH+) or a full pregnancy history (FPH). A sub-sample across both groups were asked additional stillbirth questions. Questions were evaluated using descriptive measures. Using an interpretative paradigm and phenomenology methodology, focus group discussions with women exploring barriers to reporting birthweight for stillbirths were conducted. Thematic analysis was guided by an a priori codebook., Results: Overall 69,176 women reported 98,483 livebirths (FBH+) and 102,873 pregnancies (FPH). Additional questions were asked for 1453 stillbirths, 1528 neonatal deaths and 12,620 surviving children born in the 5 years prior to the survey. Completeness was high (> 99%) for existing FBH+/FPH questions on signs of life at birth and gestational age (months). Discordant responses in signs of life at birth between different questions were common; nearly one-quarter classified as stillbirths on FBH+/FPH were reported born alive on additional questions. Availability of information on gestational age (weeks) (58.1%) and birthweight (13.2%) was low amongst stillbirths, and heaping was common. Most women (93.9%) were able to report the sex of their stillborn baby. Response completeness for stillbirth timing (18.3-95.1%) and estimated proportion intrapartum (15.6-90.0%) varied by question and site. Congenital malformations were reported in 3.1% stillbirths. Perceived value in weighing a stillborn baby varied and barriers to weighing at birth a nd knowing birthweight were common., Conclusions: Improving stillbirth data in surveys will require investment in improving the measurement of vital status, gestational age and birthweight by healthcare providers, communication of these with women, and overcoming reporting barriers. Given the large burden and effect on families, improved data must be made available to end preventable stillbirths.

Background: Household surveys remain important sources of maternal and child health data, but until now, standard surveys such as Demographic and Health Surveys (DHS) have not collected information on maternity care for women who have experienced a stillbirth. Thus, nationally representative data are lacking to inform programmes to address the millions of stillbirths which occur annually., Methods: The EN-INDEPTH population-based survey of women of reproductive age was undertaken in five Health and Demographic Surveillance System sites in Bangladesh, Ethiopia, Ghana, Guinea-Bissau and Uganda (2017-2018). All women answered a full birth history with additional questions on pregnancy losses (FBH+) or full pregnancy history (FPH). A sub-sample, including all women reporting a recent stillbirth or neonatal death, was asked additional maternity care questions. These were evaluated using descriptive measures. Associations between stillbirth and maternal socio-demographic characteristics, babies' characteristics and maternity care use were assessed using a weighted logistic regression model for women in the FBH+ group., Results: A total of 15,591 women reporting a birth since 1 January 2012 answered maternity care questions. Completeness was very high (> 99%), with similar proportions of responses for both live and stillbirths. Amongst the 14,991 births in the FBH+ group, poorer wealth status, higher parity, large perceived baby size-at-birth, preterm or post-term birth, birth in a government hospital compared to other locations and vaginal birth were associated with increased risk of stillbirth after adjusting for potential confounding factors. Regarding association with reported postnatal care, women with a stillbirth were more likely to report hospital stays of > 1 day. However, women with a stillbirth were less likely to report having received a postnatal check compared to those with a live birth., Conclusions: Women who had experienced stillbirth were able to respond to questions about pregnancy and birth, and we found no reason to omit questions to these women in household surveys. Our analysis identified several potentially modifiable factors associated with stillbirth, adding to the evidence-base for policy and action in low- and middle-income contexts. Including these questions in DHS-8 would lead to increased availability of population-level data to inform action to end preventable stillbirths.

Background: Universal vaccination and antiviral therapy have reduced chronic hepatitis B virus (HBV) in natives in the Western world. However, immigration from high HBV endemic areas continues to maintain a relatively stable prevalence of chronic hepatitis B in most developed countries., Methods: All foreigners attending a referral infectious diseases department in Madrid, Spain, from January 2007 to December 2008, were evaluated for serum HBV surface antigen (HBsAg). Positive cases underwent further virological characterization., Results: A total of 1718 foreigners were examined, of whom 1322 (77%) were sub-Saharan Africans. Serum HBsAg was positive in 121 (7%), HIV in 135 (7.9%) and hepatitis C virus antibodies in 212 (12.3%). HBV subgenotype A3, which so far had only been reported in people originating from Cameroon, was found in nearly half (14/29) of the tested specimens with detectable serum HBV-DNA. Interestingly, the lamivudine resistance mutation rtM204V was found in two Africans (6.9%), one infected with HBV-A3 and the other with HBV-E. Lack of prior exposure to antiviral therapy in these two patients was confirmed retrospectively., Conclusions: Circulation of uncommon HBV variants, including strains with primary drug resistance, may follow large immigrant flows from HBV endemic regions to Western countries. Close surveillance of this population is warranted, as early diagnosis and early antiviral therapy may reduce transmission and prevent clinical complications.

Chronic hepatitis B virus (HBV) infection is recognized in 5% to 10% of persons with HIV. Co-infected individuals show an accelerated course of HBV-associated liver disease with faster progression to cirrhosis. The number of anti-HBV drugs has increased in the past few years, and some agents (eg, lamivudine, emtricitabine, tenofovir) also exert activity against HIV-1. Emergence of drug resistance challenges the long-term benefit of anti-HBV monotherapy. Data derived from studies using new more potent anti-HBV drugs are very promising, and strategies to use these antiretrovirals sequentially or in combination are being developed. Appropriate diagnosis and monitoring of chronic hepatitis B, including the use of noninvasive tools for assessing liver fibrosis, measurement of serum HBV-DNA, and drug-resistance testing, along with wise use of antivirals may convert HBV/HIV co-infection in to a manageable disease. Hopefully, this success will translate into a halt of liver-related complications and death in the co-infected population.

Background: Chronic hepatitis C virus (HCV) infection remains a global health threat with approximately 200 million carriers worldwide. Current treatment consists of the use of peginterferon (pegIFN)/ribavirin (RBV) for 24 or 48 weeks depending on HCV genotype. Serious side effects and the fact that less than half of patients infected with HCV genotypes 1 and 4 (which are the most common) accomplish sustained virological response with this medication warrant the need for novel anti-HCV therapies., Objective: Description of specifically targeted antiviral therapies for hepatitis C (STAT-C) designed to inhibit the serine protease and the RNA-dependent HCV-RNA polymerase., Methods: Review of available data reported in peer-reviewed journals and medical conferences., Results/conclusions: Early preclinical studies using these compounds produced encouraging results, but the initial enthusiasm has been hampered by toxicity issues and rapid selection of resistance. Therefore, combination therapy with a backbone of pegIFN/RBV, or perhaps in the future using several of these small molecules, preferably having distinct modes of action and resistance profiles, will be required.

Background and Aim: Resistance to lamivudine therapy of chronic hepatitis B virus (HBV) infection occurs by mutation in the YMDD motif of the reverse transcriptase (rt) domain (rtM204V/I) of the virus polymerase, and is usually accompanied by rtL180M mutation. Here we investigated virological factors associated with hepatic failure in a 58-year-old male, chronically HBV-infected patient who died after 33 months of lamivudine therapy., Methods: Nucleotide sequencing was performed from one sample collected before and two samples collected during lamivudine therapy., Results: A peak of alanine aminotransferase and aspartate aminotransferase levels occurred after 19 months of lamivudine treatment, associated with the rtM204I mutation. After 32 months, the rtM204V mutation was predominant, accompanied by the lamivudine-resistant rtL180M mutation. Furthermore, two rare polymerase (rtS117Y and rtV142A) and three HBsAg (L109I, F134L, and I208T) substitutions were observed. At that time, the patient was hospitalized with hepatic decompensation, followed by hepatic failure, and died one month later. HBV-DNA was detected at moderate levels (8.3 x 10(4)-2.6 x 10(6) copies/mL) throughout., Conclusion: The results suggest that substitutions in polymerase (rtS117Y, rtV142A) and surface antigens (L109I, F134L, and I208T), associated with lamivudine-resistant mutations at positions 180 and 204, were involved in this case of fatal hepatitis B.

Background: Hepatitis delta virus (HDV) has a unique replication process that requires coinfection with hepatitis B virus (HBV). Treatment is currently limited to interferon therapy. The role of potent nucleos(t)ide analogues active against HBV has not been well examined in chronic delta hepatitis (CDH)., Methods: HIV-positive patients with CDH attending our hospital were identified and longitudinally studied. Serum HBV DNA, HDV RNA and HIV RNA, treatment regimens, and biochemical and serological markers were assessed at yearly intervals. Liver fibrosis was measured by transient elastography during the last 2 years., Results: Sixteen patients were identified and treated with anti-HBV therapy (median time 6.1 years). The majority were male and previous intravenous drug users. Median baselines were: HDV RNA 7 log10 copies/ml, HIV RNA 1.7 log10 copies/ml, HBV DNA 1.1 log10 IU/ml and alanine aminotransferase (ALT) 98 IU/ml. A significant correlation was found between HDV RNA and HBV DNA (r=0.226, P=0.015), aspartate aminotransferase (r=0.430, P<0.0001), ALT (r=0.441, P<0.0001) and hepatitis B surface antigen (HBsAg) (r=0.557, P<0.0001). Overall, 13 patients showed a reduction in HDV viraemia and ALT levels, and three of them achieved undetectable HDV RNA and normal ALT levels., Conclusion: Patients undergoing successful anti-HBV therapy with potent nucleos(t)ide analogues seem to indirectly benefit from suppression of HDV replication, albeit not very efficiently. Hypothetically, a significant and sustained reduction in serum HDV RNA might only be seen when a reduction in HBV covalently closed circular DNA or HBV surface antigen is achieved, which may require long periods of successful anti-HBV therapy. To our knowledge, this is the first evidence of the benefit of potent anti-HBV nucleos(t)ide analogue therapy in CDH.

Purpose of Review: Around 10% of individuals infected with HIV suffer from chronic hepatitis B virus infection. This represents at least 4 million people worldwide. HIV infection modifies the course of hepatitis B virus associated liver disease with faster progression to cirrhosis. The number of anti-hepatitis B virus drugs has increased within the last few years, and some of them also exert activity against HIV-1. The aim of this article is to update the current knowledge on antiviral therapy for chronic hepatitis B in HIV-infected patients., Recent Findings: In the absence of successful anti-hepatitis B virus therapy, morbidity and mortality associated with liver disease are increased in hepatitis B virus/HIV coinfected individuals. Data derived from studies using new more potent anti-hepatitis B virus drugs are very promising, and strategies to use these antivirals sequentially and/or in combination are being developed. Hopefully, this success will help bring a halt to liver-related complications and death in the hepatitis B virus/HIV coinfected population., Summary: Appropriate diagnosis and monitoring of chronic hepatitis B, including the use of noninvasive tools for assessing liver fibrosis, measurement of serum hepatitis B virus-DNA, and drug resistance testing, along with wise use of antivirals may convert hepatitis B virus/HIV coinfection into a manageable disease.

To assess the results from lamivudine treatment (100 mg or 150 mg) for chronic hepatitis B, 34 patients were followed at a clinic in Cuiabá, Mato Grosso, Central Brazil. Among them, 21 (62%) had liver cirrhosis and 24 (70%) were HBeAg-positive. The viral genotype was determined for 18 patients, among whom genotype A was the most prevalent (12). The median follow-up was 27 months (range from 7 to 64 months). Among the total, 23 (67%) presented a biochemical response after 2 to 24 months of treatment. Among the 24 HBeAg-positive subjects, 13 (54%) became HBeAg-negative during the follow-up. Among the anti-HBe-positive patients, 70% obtained normalization of aminotransferase levels. Fourteen (41%) did not present any initial biochemical or serological response or presented breakthrough. The L180M and M204V mutations were found in six of the non-responders. Four patients died after at least 21 months of lamivudine and three patients with liver cirrhosis developed liver cancer after 24 months. From the third year onwards, complications such as digestive system hemorrhage or liver cancer started to emerge. The present findings suggest that an early response to lamivudine treatment may be associated with better control over chronic hepatitis B.