Tuberculosis contact tracing, Angola.

Objective: To assess the outcomes of a contact-tracing programme to increase the diagnosis of tuberculosis in Cubal, Angola and offer preventive treatment to high-risk groups. Methods: A health centre-based contact-tracing programme was launched in Hospital Nossa Senhora da Paz in March 2015 and we followed the programme until 2022. In that time, staffing and testing varied which we categorized as four periods: medical staff reinforcement, 2015-2017, with a doctor seconded from Vall d'Hebron University Hospital, Spain; routine staff, 2017-2021, with no external medical support; community directly observed treatment (DOT), 2018-2019 with community worker support; and enhanced contact tracing, 2021-2022, with funding that allowed free chest radiographs, molecular and gastric aspirate testing. We assessed differences in contacts seen each month, and testing and treatment offered across the four periods. Findings: Overall, the programme evaluated 1978 contacts from 969 index cases. Participation in the programme was low, although it increased significantly during the community DOT period. Only 16.6% (329/1978) of contacts had a chest radiograph. Microbiological confirmation increased to 72.2% (26/36) after including molecular testing, and 10.1% (200/1978) of contacts received treatment for tuberculosis. Of 457 contacts younger than 5 years, 36 (7.9%) received preventive tuberculosis treatment. Half of the contacts were lost to follow-up before a final decision was taken on treatment. Conclusion: Contact tracing increased the diagnosis of tuberculosis although engagement with the programme was low and loss to follow-up was high. Participation increased during community DOT. Community-based screening should be explored to improve participation and diagnosis.

Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial.

BACKGROUND: Treatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease. METHODS: The MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain. We included participants aged 18 years and older diagnosed with Chagas disease with two different serological tests and detectable T cruzi DNA by qPCR in blood. Previously treated people, pregnant women, and people with severe cardiac forms were excluded. Participants were randomly assigned 1:1:1, using a balanced block randomisation scheme stratified by country, to receive benznidazole at three different doses: 300 mg/day for 60 days (control group), 150 mg/day for 60 days (low dose group), or 400 mg/day for 15 days (short treatment group). The primary outcome was the proportion of patients with a sustained parasitological negativity by qPCR during a follow-up period of 12 months. The primary safety outcome was the proportion of people who permanently discontinued the treatment. Both primary efficacy analysis and primary safety analysis were done in the intention-to-treat population. The trial is registered with EudraCT, 2016-003789-21, and ClinicalTrials.gov, NCT03191162, and is completed. FINDINGS: From April 20, 2017, to Sept 20, 2020, 245 people were enrolled, and 234 were randomly assigned: 78 to the control group, 77 to the low dose group, and 79 to the short treatment group. Sustained parasitological negativity was observed in 42 (54%) of 78 participants in the control group, 47 (61%) of 77 in the low dose group, and 46 (58%) of 79 in the short treatment group. Odds ratios were 1·41 (95% CI 0·69-2·88; p=0·34) when comparing the low dose and control groups and 1·23 (0·61-2·50; p=0·55) when comparing short treatment and control groups. 177 participants (76%) had an adverse event: 62 (79%) in the control group, 56 (73%) in the low dose group, and 59 (77%) in the short treatment group. However, discontinuations were less frequent in the short treatment group compared with the control group (2 [2%] vs 11 [14%]; OR 0·20, 95% CI 0·04-0·95; p=0·044). INTERPRETATION: Participants had a similar parasitological responses. However, reducing the usual treatment from 8 weeks to 2 weeks might maintain the same response while facilitating adherence and increasing treatment coverage. These findings should be confirmed in a phase 3 clinical trial. FUNDING: European Community's 7th Framework Programme.

Impact of traditional cutaneous scarification on anthrax lesions: A series of cases from Cubal, Angola.

OBJECTIVES: Bacillus anthracis infection is a worldwide zoonosis that affects the most vulnerable population and has a high mortality rate without treatment, especially in non-cutaneous presentations. Cutaneous scarification is still common in some regions of the world for the treatment of certain diseases as part of traditional medicine. We describe a series of cutaneus anthrax from a rural setting in Angola where cutaneus scarification is common. CASE PRESENTATION: This is a retrospective observational study describing a series of cutaneous anthrax cases from Cubal (Angola), many of whom were treated with skin scarification before admission. A total of 26 cases were diagnosed from January 2010 to December 2018. None of the cases were confirmed and eight (30.8%) were probable cases according to the Centers for the Disease Control and Prevention anthrax case definition. The median age was 11 (4.7-30.5) years, 17 (65.4%) had lesions on the head, face, or neck and 15 (57.7%) were treated with cutaneous scarification. Nine (34.6%) patients died. Traditional cutaneous scarification was significantly associated with cutaneous superinfection, respiratory, systemic involvement, and death. CONCLUSION: Our case series points to increased complications and worse outcome of cutaneous anthrax disease if treated with skin scarification.

Adherence and Toxicity during the Treatment of Latent Tuberculous Infection in a Referral Center in Spain.

The screening and treatment of latent tuberculosis infection (LTBI) in countries with a low incidence of TB is a key strategy for the elimination of tuberculosis (TB). However, treatment can result in adverse events (AEs) and have poor adherence. This study aimed to describe treatment outcomes and AEs for LTBI patients at two departments in Vall d'Hebron University Hospital in Barcelona, Spain. A retrospective study was conducted on all persons treated for LTBI between January 2018 and December 2020. Variables collected included demographics, the reason for LTBI screening and treatment initiation, AEs related to treatment, and treatment outcome. Out of 261 persons who initiated LTBI treatment, 145 (55.6%) were men, with a median age of 42.1 years. The indications for LTBI screening were household contact of a TB case in 96 (36.8%) persons, immunosuppressive treatment in 84 (32.2%), and recently arrived migrants from a country with high TB incidence in 81 (31.0%). Sixty-three (24.1%) persons presented at least one AE during treatment, and seven (2.7%) required definitive discontinuation of treatment. In the multivariate analysis, AE development was more frequent in those who started LTBI treatment due to immunosuppression. Overall, 226 (86.6%) completed treatment successfully. We concluded that LTBI screening and treatment groups had different risks for adverse events and treatment outcomes. Persons receiving immunosuppressive treatment were at higher risk of developing AEs, and recently arrived immigrants from countries with a high incidence of TB had greater LTFU. A person-centered adherence and AE management plan is recommended.

Post-infectious irritable bowel syndrome following a diagnosis of traveller's diarrhoea: a comprehensive characterization of clinical and laboratory parameters.

BACKGROUND: Prolonged or recurrent gastrointestinal symptoms may persist after acute traveller's diarrhoea (TD), even after adequate treatment of the primary cause. This study aims to describe the epidemiological, clinical and microbiological characteristics of patients with post-infectious irritable bowel syndrome (PI-IBS) after returning from tropical or subtropical areas. METHODS: We conducted a retrospective study of patients presenting between 2009 and 2018 at the International Health referral centre in Barcelona with persistent gastrointestinal symptoms following a diagnosis of TD. PI-IBS was defined as the presence of persistent or recurrent gastrointestinal manifestations for at least 6 months after the diagnosis of TD, a negative stool culture for bacterial pathogens and a negative ova and parasite exam after targeted treatment. Epidemiological, clinical and microbiological variables were collected. RESULTS: We identified 669 travellers with a diagnosis of TD. Sixty-eight (10.2%) of these travellers, mean age 33 years and 36 (52.9%) women, developed PI-IBS. The most frequently visited geographical areas were Latin America (29.4%) and the Middle East (17.6%), with a median trip duration of 30 days (IQR 14-96). A microbiological diagnosis of TD was made in 32 of these 68 (47%) patients, 24 (75%) of whom had a parasitic infection, Giardia duodenalis being the most commonly detected parasite (n = 20, 83.3%). The symptoms persisted for a mean of 15 months after diagnosis and treatment of TD. The multivariate analysis revealed that parasitic infections were independent risk factors for PI-IBS (OR 3.0, 95%CI 1.2-7.8). Pre-travel counselling reduced the risk of PI-IBS (OR 0.4, 95%CI 0.2-0.9). CONCLUSIONS: In our cohort, almost 10% of patients with travellers' diarrhoea developed persistent symptoms compatible with PI-IBS. Parasitic infections, mainly giardiasis, seem to be associated with PI-IBS.

Civil Engineering and Malaria Risk: A Descriptive Study in a Rural Area of Cubal, Angola.

(1) Background: Angola is among the high-burden countries with malaria cases globally. After 2013, we suspected an increase in the number of malaria cases in Cubal (Angola), previously in decline. Our objective was to evaluate the incidence rate in Cubal, overall and by neighborhood, for 2014, 2015, and 2016. (2) Methods: A retrospective, observational study was performed in Cubal (Angola) from January 2014 to December 2016, including all patients with a microbiologically confirmed diagnosis, treated at Cubal's Hospitals for this period of time. The principal variables calculated were the incidence rates of 2014, 2015, and 2016 in Cubal (overall and by neighborhood). (3) Results: There were 3249 malaria cases. The incidence rates were 2.27, 10.73, and 12.40 cases per 1000 inhabitants in 2014, 2015, and 2016, respectively. In the neighborhood, Hamavoko-Kasseke, there was a 10.73-fold increase in incidence during this period. Additionally, Hamavoko-Kasseke presents an anomalous distribution of malaria cases. (4) Conclusions: We observed an increase in the incidence of malaria in Cubal during the three-year study period. The case distribution was highly heterogeneous with hyperendemic areas, and we found a chronobiological association between the construction of a civil engineering project. This information could be useful for deciding which malaria control strategies must be implemented in this area.

Evaluation of Two Different Strategies for Schistosomiasis Screening in High-Risk Groups in a Non-Endemic Setting.

A consensus on the recommended screening algorithms for schistosomiasis in asymptomatic high-risk subjects in non-endemic areas is lacking. The objective of this study was to evaluate the real-life performance of direct microscopy and ELISA serology for schistosomiasis screening in a high-risk population in a non-endemic setting. A retrospective cohort study was conducted in two out-patient Tropical Medicine units in Barcelona (Spain) from 2014 to 2017. Asymptomatic adults arriving from the Sub-Saharan region were included. Schistosomiasis screening was conducted according to clinical practice following a different strategy in each setting: (A) feces and urine direct examination plus S. mansoni serology if non-explained eosinophilia was present and (B) S. mansoni serology plus uroparasitological examination as the second step in case of a positive serology. Demographic, clinical and laboratory features were collected. Schistosomiasis cases, clinical management and a 24 month follow-up were recorded for each group. Four-hundred forty individuals were included. The patients were mainly from West African countries. Fifty schistosomiasis cases were detected (11.5% group A vs. 4 % group B, p = 0.733). When both microscopic and serological techniques were performed, discordant results were recorded in 18.4% (16/88). Schistosomiasis cases were younger (p < 0.001) and presented eosinophilia and elevated IgE (p < 0.001) more frequently. Schistosomiasis is a frequent diagnosis among high-risk populations. Serology achieves a similar performance to direct diagnosis for the screening of schistosomiasis in a high-risk population.

Case Report: Leishmaniasis in a 33-Year-Old Man with Multiple Sclerosis.

Leishmaniasis is a protozoan disease caused by species of genus Leishmania. Immunosuppression increases the risk of severe clinical forms and impairs response to treatment. The expansion of the use of immunomodulatory drugs for different conditions has raised the number of these cases. In this report, we present a case of visceral leishmaniasis in a patient with multiple sclerosis (MS) under fingolimod treatment. He presented with the triad of fever, visceromegaly, and pancytopenia and was diagnosed by the presence of amastigotes in a bone marrow sample. Furthermore, we discuss the previous published cases of MS patients under different immunosuppressant therapies to highlight its risk in endemic areas and suggest a therapeutic approach.

MDR Tuberculosis Treatment.

Multidrug-resistant (MDR) tuberculosis (TB), resistant to isoniazid and rifampicin, continues to be one of the most important threats to controlling the TB epidemic. Over the last few years, there have been promising pharmacological advances in the paradigm of MDR TB treatment: new and repurposed drugs have shown excellent bactericidal and sterilizing activity against Mycobacterium tuberculosis and several all-oral short regimens to treat MDR TB have shown promising results. The purpose of this comprehensive review is to summarize the most important drugs currently used to treat MDR TB, the recommended regimens to treat MDR TB, and we also summarize new insights into the treatment of patients with MDR TB.

Frequency and characteristics of HTLV in migrants: results from the +Redivi collaborative network in Spain.

INTRODUCTION: The objective of this study was to describe the main characteristics of migrants diagnosed with human T-lymphotropic virus (HTLV) infection within the +Redivi Spanish network. METHODS: Patients with a diagnosis of HTLV type 1 or 2 in +Redivi from October 2009 to December 2020 were included. Diagnosis was based on positive HTLV serology (enzyme-linked immunosorbent assay (ELISA)/chemiluminescent immunoassay (CLIA)) with line immunoassay (LIA)/Western blot with/without polymerase chain reaction (PCR). RESULTS: A total of 107/17 007 cases (0.6%) had a final diagnosis of HTLV infection: 83 (77.67%) HTLV-1 infections, 6 (5.6%) HTLV-2 infections and 18 (16.8%) non-specified. The majority (76, 71%) were female, median age was 42 years and median time from arrival to Spain until consultation was 10 years. The group included 100 (93.5%) immigrants and 7 (6.6%) visiting friends and relatives (VFR)-immigrants. Most patients were from South America (71, 66.4%), followed by Sub-Saharan Africa (15, 14%) and Central America-Caribbean (13, 12.1%). Around 90% of patients were asymptomatic at presentation and diagnosed as part of screening programs. Median duration of follow-up was 5 years (IQR 2-7). Regarding HTLV-associated conditions, 90 patients (84.2%) had none, 7 (6.5%) had tropical spastic paraparesis , 5 (4.7%) had other associated conditions (dermatitis, uveitis, pulmonary disease), 3 (2.8%) had other neurological symptoms and 2 (1.9%) had adult T-cell leukaemia/lymphoma. No patients with HTLV-2 had HTLV-associated conditions. Four patients (3.7%) died. Concomitant diagnoses were found in 41 (38.3%) patients, including strongyloidiasis in 15 (14%) and HIV co-infection in 4 (3.7%). In 70% of patients, screening of potential contacts was not performed/recorded. CONCLUSIONS: HTLV infections (the majority due to HTLV-1) were mainly diagnosed in asymptomatic migrants from Latin America (generally long-settled immigrants and the majority female with the consequent implications for screening/prevention). A high rate of association with strongyloidiasis was found. In the majority, screening of potential contacts was not performed, representing a missed opportunity for decreasing the under diagnosis of this infection.

Epidemiological and clinical profile of adult patients with diarrhoea after international travel attended in an International Health referral center.

BACKGROUND: The aim of the study is to describe the epidemiological, clinical, and microbiological characteristics of patients with diarrhoea after their return from a trip to tropical and subtropical areas. METHODS: Retrospective study of patients with travel-related diarrhoea attended International Health referral center. Travel diarrhoea was defined as the presence of three or more liquid stools per day, or liquid stools more often than is normal for the individual, during travel or within two weeks after returning. Epidemiological, clinical and microbiological variables were collected. RESULTS: 669 patients were included, 393 (58.7%) were female, with a mean age of 33 (SD 10.7) years. Abdominal pain was present in 59.6% (n = 399), and fever in 44.7% (n = 299). In 43% (n = 280) cases the etiological agent was found. Giardia duodenalis, Enteropathogenic Escherichia coli, and Enterotoxigenic Escherichia coli were the most frequent identified causative agents. Parasitic cause of the diarrhoea was associated to a longer duration of the travel, longer duration of symptoms, and having received pre-travel counseling. CONCLUSIONS: In our cohort, that represents a group of travellers presenting prolonged symptoms after travel, the most frequent causes of diarrhoea were parasitic infections being the most prevalent Giardia duodenalis. This information could be relevant in order to improve travel-related diarrhoea management protocols in this type of patients.

COVID-19 Clinical Profile in Latin American Migrants Living in Spain: Does the Geographical Origin Matter?

The aim of this study was to describe and compare the clinical characteristics of hospitalized patients with COVID-19 pneumonia according to their geographical origin. This is a retrospective case-control study of hospitalized patients with confirmed COVID-19 pneumonia treated at Vall d'Hebron University Hospital (Barcelona) during the first wave of the pandemic. Cases were defined as patients born in Latin America and controls were randomly selected among Spanish patients matched by age and gender. Demographic and clinical variables were collected, including comorbidities, symptoms, vital signs and analytical parameters, intensive care unit admission and outcome at 28 days after admission. Overall, 1080 hospitalized patients were registered: 774 (71.6%) from Spain, 142 (13.1%) from Latin America and the rest from other countries. Patients from Latin America were considered as cases and 558 Spanish patients were randomly selected as controls. Latin American patients had a higher proportion of anosmia, rhinorrhea and odynophagia, as well as higher mean levels of platelets and lower mean levels of ferritin than Spanish patients. No differences were found in oxygen requirement and mortality at 28 days after admission, but there was a higher proportion of ICU admissions (28.2% vs. 20.2%, p = 0.0310). An increased proportion of ICU admissions were found in patients from Latin America compared with native Spanish patients when adjusted by age and gender, with no significant differences in in-hospital mortality.

Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola.

BACKGROUND: The importance of Mycobacterium tuberculosis strains with disputed rpoB mutations remains to be defined. This study aimed to assess the frequency and types of rpoB mutations in M. tuberculosis isolates from Cubal, Angola, a country with a high incidence of tuberculosis. METHODS: All isolates included (n = 308) were analyzed using phenotypic drug susceptibility testing and GenoType MTBDRplus assay. DNA sequencing of the rpoB gene and determination of rifampicin MIC by macrodilution method were additionally performed on isolates yielding discordant results (n = 12) and those in which the mutation detected was not characterized (n = 8). RESULTS: In total, 85.1% (74/87) of rifampicin-resistant strains had undisputed rpoB mutations -S450L (49), D435V (15), H445D (3), H445Y (2), Q432ins (1), L449M plus S450F (1), S450F (1), S450W (1) and S450Y (1)-; 10.3% (9/87) had disputed rpoB mutations-L430P plus S493L (1), N437del (1), H445L (3), D435Y (2), L452P (2)-, 2.3% (2.3%) showed no rpoB mutations and 2.3% (2/87) showed heteroresistance-D435Y plus L452P and L430P plus S493L-. CONCLUSION: Disputed rpoB mutations were common, occurring in 10.3% of rifampicin resistant isolates. Current phenotyping techniques may be unable to detect this resistance pattern. To increase their sensitivity, a lower concentration of RIF could be used in these tests or alternatively, rpoB mutations could be screened and characterized in all M. tuberculosis strains.

Telemedicine experience between two hospitals from Angola and Spain.

OBJECTIVE: Telemedicine uses information and communication technologies to provide services in the field where the distance is a critical factor. The aim of the present study is to describe the experience of a synchronous telemedicine between two hospitals in Spain and Angola. METHODS: This is a retrospective observational study of all synchronous telemedicine sessions conducted between the Hospital Nossa Senhora da Paz in Angola and the Vall d'Hebron University Hospital in Spain from January 2011 to December 2014. RESULTS: Seventy-two cases were discussed in the telemedicine sessions. The average age of patients was 18.02 (SD 13.75) years and mostly women (54.38 percent). Reasons to discuss the cases were 46.47 percent doubts in the diagnosis and therapeutic management, 15.47 percent were purely formative cases, and only 8.45 percent treatment doubt. At the time of presentation, 29 percent of the patients were already diagnosed, 95 percent of whom with infectious disease diagnostic, and from the undiagnosed patients 36 percent presented a febrile syndrome. CONCLUSION: This study shows the viability of synchronous telemedicine between European and African countries without an excessively sophisticated technology.

Aportaciones de las técnicas moleculares en la fase crónica de la Enfermedad de Chagas en ausencia de tratamiento / Contributions of molecular techniques in the chronic phase of Chagas disease in the absence of treatment

INTRODUCCIÓN: La fase crónica de la enfermedad de Chagas se caracteriza por una parasitemia baja e intermitente. En esta fase la sensibilidad de la reacción en cadena de la polimerasa (PCR) es muy variable, limitando su utilización como técnica diagnóstica. A pesar de ello, la realización de la PCR en pacientes no tratados puede aportar datos sobre el comportamiento del parásito y su presencia en sangre periférica. MÉTODOS: Se realizó PCR a tiempo real de forma puntual en una cohorte de 495 pacientes con enfermedad de Chagas crónica en ausencia de tratamiento. También se realizó seguimiento de una subcohorte de 29 pacientes mediante PCR a tiempo real seriadas, entre 8 y 12 meses en los que no tuvieron acceso al tratamiento por falta de suministro. RESULTADOS: El porcentaje de positividad de PCR a tiempo real fue de 42%. Este porcentaje fue significativamente mayor en pacientes con 5 años o menos de residencia en España (p = 0,041). La detección de ADN no se relacionó con la existencia de alteraciones cardíacas y/o digestivas. En el subgrupo de pacientes a los que se realizaron determinaciones seriadas, el resultado de PCR fue sostenidamente positivo en el 13,8% de los pacientes, negativo en el 31% e intermitente en el 55,2%. CONCLUSIONES: Las diferencias de resultados de PCR a tiempo real en función del tiempo de residencia apuntan que existen factores externos que pueden influir en la presencia del parásito en sangre periférica. Así mismo, factores propios del hospedador parecen influir en la dinámica parasitaria a lo largo del tiempo

INTRODUCTION: The chronic phase of Chagas disease (CD) is characterised by a low and intermittent parasitaemia. The Polymerase Chain Reaction (PCR) presents a variable sensitivity in this stage limiting its use as a diagnostic tool. Despite this, the use of PCR in untreated patients can provide information on the parasite behaviour and its presence in peripheral blood. METHODS: A timely real-time PCR determination was performed on a cohort of 495 untreated chronic CD patients. Also, a subcohort of 29 patients was followed-up by serial real-time PCR during a period from 8 to 12 months in which they could not have access to the treatment due to lack of supply. RESULTS: The positive percentage of real-time PCR in our series was 42%. Nevertheless, real-time PCR positive results were significantly higher in patients with five years or less of residence in Spain (P = .041). The detection of DNA was not related to the existence of cardiac and/or gastrointestinal abnormalities. In the follow-up subgroup, real-time PCR was consistently positive in 13.8% of patients, consistently negative in 31%, and intermittent in 55.2%. CONCLUSIONS: The different real-time PCR results regarding the time of residence suggests the possible relationship of external factors in the parasite presence in peripheral blood. On the other hand, specific host factors may be involved in the behaviour of parasitaemia over time

Beta-Hemolytic Streptococcal Infective Endocarditis: Characteristics and Outcomes From a Large, Multinational Cohort.

BACKGROUND: Beta-hemolytic streptococci (BHS) are an uncommon cause of infective endocarditis (IE). The aim of this study was to describe the clinical features and outcomes of patients with BHS IE in a large multinational cohort and compare them with patients with viridans streptococcal IE. METHODS: The International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) is a large multinational database that recruited patients with IE prospectively using a standardized data set. Sixty-four sites in 28 countries reported patients prospectively using a standard case report form developed by ICE collaborators. RESULTS: Among 1336 definite cases of streptococcal IE, 823 were caused by VGS and 147 by BHS. Patients with BHS IE had a lower prevalence of native valve (P < .005) and congenital heart disease predisposition (P = .002), but higher prevalence of implantable cardiac device predisposition (P < .005). Clinically, they were more likely to present acutely (P < .005) and with fever (P = .024). BHS IE was more likely to be complicated by stroke and other systemic emboli (P < .005). The overall in-hospital mortality of BHS IE was significantly higher than that of VGS IE (P = .001). In univariate analysis, variables associated with in-hospital mortality for BHS IE were age (odds ratio [OR], 1.044; P = .004), prosthetic valve IE (OR, 3.029; P = .022), congestive heart failure (OR, 2.513; P = .034), and stroke (OR, 3.198; P = .009). CONCLUSIONS: BHS IE is characterized by an acute presentation and higher rate of stroke, systemic emboli, and in-hospital mortality than VGS IE. Implantable cardiac devices as a predisposing factor were more often found in BHS IE compared with VGS IE.