Prevalence of sexually transmitted infections (STIs), associations with sociodemographic and behavioural factors, and assessment of the syndromic management of vaginal discharge in women with urogenital complaints in Mozambique.

In Mozambique, sexually transmitted infections (STIs) are estimated to be prevalent, but diagnosis and treatment of curable STIs rely only on syndromic management. We examined the prevalence of four non-viral STIs and HIV-1/2, based on etiological diagnosis, associations with sociodemographic and behavioural factors, and the STI diagnostic accuracy of the vaginal discharge syndromic management in women with urogenital complaints in Maputo, Mozambique. A cross-sectional study was performed in Maputo, Mozambique, February 2018-January 2019, enrolling 924 women of reproductive age with urogenital complaints. Endocervical/vaginal swabs were sampled and chlamydia, gonorrhoea, trichomoniasis and Mycoplasma genitalium infections were diagnosed using a multiplex real-time PCR (AmpliSens; InterLabServices). Serological testing was performed for HIV-1/2. A structured questionnaire collected metadata. All data were analyzed in STATA/IC 12.1 using descriptive statistics, chi-square tests and logistic regression model. About 40% of the women were less than 24 years old, 50.8% were single, 62.1% had their sexual debut between 12 and 17 years of age, and the main complaint was vaginal discharge syndrome (85%). The prevalence of chlamydia was 15.5%, trichomoniasis 12.1%, gonorrhoea 4.0%, M. genitalium 2.1%, and HIV-1/2 22.3%. The vaginal discharge syndrome flowchart had a sensitivity of 73.0%-82.5% and a specificity of 14%-15% for the detection of any individual non-viral STI in women with urogenital complaints. In total, 19.2% of the symptomatic women with chlamydia, trichomoniasis or gonorrhoea would not be detected and accordingly treated using the vaginal discharge syndromic management (missed treatment) and 70.0% of the women would be treated despite not being infected with any of these three STIs (overtreatment). In conclusion, a high prevalence of especially chlamydia, trichomoniasis, and HIV-1/2 was found in women of childbearing age with urogenital complaints in Maputo, Mozambique. Syndromic management of vaginal discharge revealed low accuracy in the detection of STIs in symptomatic women, especially low specificity, which resulted in under-treatment of STI-positive cases and incorrect or over-treatment of women with urogenital complaints, many of whom were negative for all the non-viral STIs. Etiological diagnosis is imperative for effective management of STIs in symptomatic and asymptomatic women.

Structural stability of invasion graphs for Lotka-Volterra systems.

In this paper, we study in detail the structure of the global attractor for the Lotka-Volterra system with a Volterra-Lyapunov stable structural matrix. We consider the invasion graph as recently introduced in Hofbauer and Schreiber (J Math Biol 85:54, 2022) and prove that its edges represent all the heteroclinic connections between the equilibria of the system. We also study the stability of this structure with respect to the perturbation of the problem parameters. This allows us to introduce a definition of structural stability in ecology in coherence with the classical mathematical concept where there exists a detailed geometrical structure, robust under perturbation, that governs the transient and asymptotic dynamics.

Cholera and diarrheal diseases in Cuamba District, Niassa Province, Mozambique: Systematic healthcare facility-based surveillance strengthening, characteristics of suspected cholera and diarrheal patients, and incidence of diarrheal diseases.

BACKGROUND: Mozambique is one of the countries in Africa that is continuously at risk of cholera outbreaks due to poor sanitation, hygiene, and limited access to potable water in some districts. The Mozambique Cholera Prevention and Surveillance (MOCA) project was implemented in Cuamba District, Niassa Province to prevent and control cholera outbreaks through a preemptive cholera vaccination, strengthened surveillance system for cholera and diarrheal diseases, and better understanding of cholera-related healthcare seeking behavior of local populations, which may further guide the national cholera control and prevention strategies. This article presents the surveillance component of the MOCA project. METHODOLOGY/PRINCIPAL FINDINGS: A prospective healthcare facility (HCF)-based surveillance of cholera and diarrheal disease was conducted in six HCFs in the District of Cuamba from March 2019 to December 2020. A systematic surveillance procedure has been put in place with capacity building in selected sentinel HCFs and a basic microbiology laboratory established on-site. Patients presenting with suspected cholera or other diarrheal symptoms were eligible for enrollment. Clinical data and rectal swab samples were collected for laboratory confirmation of Vibrio Cholerae and other pathogens. A total of 419 eligible patients from six HCFs were enrolled. The median age was 19.8 years with a similar age distribution between sentinel sites. The majority were patients who exhibited diarrhea symptoms not suspected of cholera (88.8%; n = 410). Among those, 59.2% (210/397) were female and 59.9% (235/392) were 15 years and above. There were 2 cholera cases, coming outside of the catchment area. The incidence of diarrheal diseases ranged from 40-103 per 100,000 population. No Vibrio cholerae was isolated among surveillance catchment population and Escherichia coli spp. (82/277; 29.6%) was the most common pathogen isolated. CONCLUSION/SIGNIFICANCE: Efforts were made to strengthen the systematic surveillance of suspected cholera with standardised patient screening, enrolment, and diagnostics. The first basic microbiology laboratory in Niassa Province established in Cuamba District under the MOCA project needs to be integrated into the national network of laboratories for sustainability. No reports of laboratory confirmed cholera cases from the surveillance catchment area may be highly related to the pre-emptive oral cholera vaccine (OCV) mass vaccination campaign conducted in 2018 and the use of drugs by local populations prior to visiting the sentinel HCFs. Continued systematic cholera surveillance is needed to closely monitor the cholera endemicity and epidemics, and further evaluate the long-term impact of this vaccination. High incidence of diarrheal illnesses needs to be addressed with improved water, sanitation, and hygiene (WaSH) conditions in Cuamba District. Efforts integrated with the prioritization of prevention measures are fundamental for the control of cholera in the country.

Phase II Trial Evaluating Olaparib Maintenance in Patients with Metastatic Castration-Resistant Prostate Cancer Responsive or Stabilized on Docetaxel Treatment: SOGUG-IMANOL Study.

The SOGUG-IMANOL trial was a phase 2, uncontrolled, Spanish multicenter study to assess the effect of maintenance treatment with olaparib on radiographic progression-free survival (PFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) who achieved partial or complete response or disease stabilization on docetaxel treatment and had a documented germline/somatic mutation in any of the homologous recombination repair (HRR) genes. Patients received olaparib 300 mg orally twice daily. From the screened population (n = 134), 26 (19.4%) somatic mutations were found, and 14 patients were included in the study. The median radiographic PFS was 11.1 (95%CI, 5.7 to 16.5) months. The median PSA-PFS was 3.5 (95%CI, 1.0 to 6.0) months, and the median clinical PFS was 14.7 (95%CI, 1.8 to 27.5 months). Clinical benefit was observed in 12 patients (85.7%, 95%CI 67.4% to 100%), including two patients with partial response and 10 with stable disease. Six patients reported grade 3-5 adverse events: asthenia (n = 3), anemia (n = 2) and neutropenia (n = 1). In this setting, olaparib has been shown to be an efficacious maintenance treatment in terms of radiographic PFS and clinical benefit, becoming a therapeutic option for some patients harboring an HRR gene mutation and in scenarios where further investigation is needed.

Diagnostic capacity for cutaneous fungal diseases in the African continent.

BACKGROUND: Cutaneous fungal infections are very common, especially in poorer communities and with intercurrent HIV infection. Determining the fungal pathogen in skin-related fungal neglected tropical diseases (NTDs) determines optimal therapy. We undertook a country survey across many African countries to determine the diagnostic capacity for skin fungal diseases. METHODS: A detailed questionnaire was delivered to country contacts to collect data on availability, frequency, and location of testing for key diagnostic procedures and followed up with 2 rounds of validation by video call and by confirmation of individual country data confirmation by email. RESULTS: Of 47 countries with data, seven (15%) and 21 (45%) do not offer skin biopsy in the public or private sector, respectively, but 22 (46%) countries do it regularly, mostly in university hospitals. Direct microscopy is often performed in 20 of 48 (42%) countries in the public sector and not done in 10 (21%). Fungal cultures are often performed in 21 of 48 (44%) countries in the public sector but not done in nine (20%) or 21 (44%) in either public or private facilities. Histopathological examination of tissue is frequently used in 19 of 48 (40%) countries but not in nine (20%) countries in the public sector. The cost of diagnostics to patients was a major limiting factor in usage. CONCLUSION: Major improvements in the availability and use of diagnostic tests for skin, hair, and nail fungal disease are urgently needed across Africa.

Pre-emptive oral cholera vaccine (OCV) mass vaccination campaign in Cuamba District, Niassa Province, Mozambique: feasibility, vaccination coverage and delivery costs using CholTool.

INTRODUCTION: Mozambique suffers from regular floods along its principal river basins and periodic cyclones that resulted in several cholera epidemics during the last decades. Cholera outbreaks in the recent 5 years affected particularly the northern provinces of the country including Nampula and Niassa provinces. A pre-emptive oral cholera vaccine (OCV) mass vaccination campaign was conducted in Cuamba District, Niassa Province, and the feasibility, costs, and vaccination coverage assessed. METHODS: WHO prequalified OCV (Euvichol-Plus), a killed whole-cell bivalent vaccine containing Vibrio cholerae O1 (classical and El Tor) and O139, was administered in two doses with a 15-day interval during 7-31 August 2018, targeting around 180 000 people aged above 1 year in Cuamba District. Microplanning, community sensitisation, and training of local public health professionals and field enumerators were conducted. Feasibility and costs of vaccination were assessed using CholTool. Vaccination coverage and barriers were assessed through community surveys. RESULTS: The administrative coverage of the first and second rounds of the campaign were 98.9% (194 581) and 98.8% (194 325), respectively, based on the available population data that estimated total 196 652 inhabitants in the target area. The vaccination coverage survey exhibited 75.9% (±2.2%) and 68.5% (±3.3%) coverage for the first and second rounds, respectively. Overall, 60.4% (±3.4%) of the target population received full two doses of OCV. Barriers to vaccination included incompatibility between working hours and campaign time. No severe adverse events were notified. The total financial cost per dose delivered was US$0.60 without vaccine cost and US$1.98 including vaccine costs. CONCLUSION: The pre-emptive OCV mass vaccination campaign in remote setting in Mozambique was feasible with reasonable full-dose vaccination coverage to confer sufficient herd immunity for at least the next 3 to 5 years. The delivery cost estimate indicates that the OCV campaign is affordable as it is comparable with Gavi's operational support for vaccination campaigns.

Mapeamento de áreas críticas de cólera em moçambique / Mapping critical cholera areas in Mozambique

Moçambique é signatário da iniciativa global para a eliminação da cólera até ao ano de 2030, estratégia voltada para a interrupção da transmissão da doença, redução da mortalidade e eliminação da cólera como problema de saúde pública. Em Moçambique, a cólera é altamente sazonal, com acentuada concentração de casos durante o período quente e chuvoso, especialmente nas províncias de Cabo Delgado, Nampula, Tete e Sofala. É neste contexto, que se conduziu a análise de situação da cólera com o objectivo de identificar e mapear todas as zonas quentes e de alto risco para a doença em todo território nacional. E através de uma análise epidemiológica multinível da cólera e da Diarréia aguda, em todos os distritos e Postos administrativos do país, com recurso a dados retrospetivos dos anos 2017 à 2021, foram identificadas as zonas quentes e de alto risco da cólera em Moçambique de que se faz a presente descrição. Os métodos para mapeamento de zonas quentes foram concebidos a partir da orientação do GTFCC para identificação de zonas quentes de cólera, revistos e adaptados ao contexto nacional. Os dados utilizados foram dos casos de cólera, casos, internamentos e óbitos por Diarréia aguda notificados a nível distrital, registados na base de dados nacional de saúde (SIS-MA) e reportados pelos sistemas de gestão de dados da vigilância epidemiológica das Direcções Provinciais de Saúde (DPS's). Uma "abordagem experimental" para inferir a ocorrência de cólera a partir da ocorrência de doença diarreica foi realizada, através de dados de doença grave e óbitos por Diarréia aguda em adultos. Uma ferramenta Excel foi desenvolvida para facilitar a entrada e análise de dados por província. Todos os distritos do país foram classificados de acordo com a carga de cólera ou doença diarreica aguda e os com elevada pontuação foram selecionados e seus postos administrativos (PA) foram mapeados. Indicadores epidemiológicos adicionais e factores de risco foram utilizados para afinar e qualificar a selecção dos PA zonas quentes ou de alto risco da cólera. Foram identificados 250 Postos administrativos críticos para intervenção no contexto da eliminação da cólera, destes 75 são zonas quentes e 175 são zonas de alto risco com uma estimativa global de 14 587 782 habitantes afectados. Neste contexto, recomenda-se conceber, validar e implementar um plano nacional de eliminação da cólera com os subplanos específicos para cada pilar anexados e estabelecer um programa nacional de eliminação da cólera.

Conditions to eliminate cholera in Mozambique - the pathway for the development of the national cholera plan.

Cholera disproportionately affects the most vulnerable segments of the population, particularly those who have low or no access to basic water, sanitation, and hygiene (WASH). Despite some improvements in WASH conditions, cholera still represents a persistent challenge in Mozambique, where outbreaks occur almost every year, with high case fatality rates, posing a threat to the country's economic development. The Government of Mozambique has started developing a revised National Cholera Plan (NCP), which aligns with "ending cholera-a global roadmap to 2030" launched by the Global Task Force on Cholera Control (GTFCC) in 2017. Ending cholera represents a critical step towards achieving the sustainable development goals and requires effective prevention and control interventions, ensuring that no one is left behind. The NCP must use a multi-sector approach and broad stakeholder collaboration with well-coordinated roles and functions of different partners to address major areas for cholera elimination - water and sanitation, health care services and management, epidemiology and surveillance, and health and hygiene promotion. Every cholera death is preventable. In this review, we reiterate the need for effective coordinated actions to control and eliminate cholera in Mozambique and decrease the cholera burden, enabling a healthy population over the generations.

Environmental bacterial and fungal contamination in high touch surfaces and indoor air of a paediatric intensive care unit in Maputo Central Hospital, Mozambique in 2018.

Background: The hospital environment serves as a reservoir of microorganisms which may be associated with healthcare-associated infections (HCAI). The study of environmental contamination with microorganisms is a method for the assessment of hospital environmental hygiene. We sought to evaluate the environmental colonisation of a national reference hospital unit, using the total aerobic colony count (ACC) and the isolated microorganisms, as assessment tools. Methods: A cross-sectional study was conducted in the Paediatric Intensive Care Unit (PICU) of the Hospital Central de Maputo during a four-week period in 2018. Surfaces and air were sampled before and after room cleaning, using swabs and passive air method. Those samples were processed at the microbiology laboratory where total ACC levels were evaluated, and microorganisms were isolated, identified and assessed for antibiotic susceptibility. Discussion: Comparison of the total median ACC of the indoor air (287 cfu/m3 before and 195 cfu/m3 after) and surfaces (0.38 cfu/cm2 before and 0.33 cfu/cm2 after) before and after room cleaning did not show significant differences (P>0.05). Microorganisms of epidemiological importance, including coagulase negative staphylococci (CoNS), Klebsiella pneumoniae and Serratia odorifera were isolated and all of these three were multi-drug resistant (MDR). Conclusion: The results showed controlled contamination levels on high touch surfaces in the patient environment and a high level of contamination of the indoor air suggesting deficiencies in the PICU environmental decontamination process. There was evidence of the presence of fungi and MDR species of epidemiological importance in the context of HCAI.

Evaluation of the Mozambique Antiretroviral Therapy (MozART) database as an antiretroviral therapy patient surveillance system, 2017-2018.

Introduction: Mozambique antiretroviral therapy is a database used to monitor patients receiving antiretroviral treatment (ART). This study's objective was to evaluate the system for the purpose to monitor patients receiving ART. Methods: data from 287,052 patients who started ART from January to December 2017 were verified, and retention in care was assessed for 2018 in Mozambique. The Centers for Disease Control and Prevention guidelines for evaluating public health surveillance systems were used to conduct the evaluation. Simplicity, flexibility, data quality, representativeness and stability attributes were evaluated. Results: a total of 93% (266,880/287,052) of patients on ART were adults ≥15 years old, and 65% (186,677/287,052) were female. The system was complex, it involved four organisations and its management was online. Data quality was moderate with 19% (1,533,885/8,037,456) of empty variable fields, 0.04% (123/287,052) observations with birth date later than the initial ART date, 0.2% (424/287,052) and 23% (68,039/287,052) with initial ART date and diagnosis date, later than the next ART pickup date. Nationally, 19%(31/161) of the districts did not have data in the information system. MozART cover health facilities with electronic patient tracking systems. Hence did not represent all patients on ART. While it was not possible to add variables of the electronic patient tracking, the system was stable as neither data or server interruptions were reported. Conclusion: the system was useful, stable, with moderate data quality, complex, not flexible and not representative. We recommend to health facilities and partners to develop and distribute procedures for data validation and completeness and report all patient tracking variables in the system.

Microbiological contamination of improved water sources, Mozambique.

Objective: To assess if water from improved sources are microbiologically safe in Niassa province, Mozambique, by examining the presence of total coliforms in different types of water sources. Methods: We conducted a cross-sectional household survey in two rural districts of Niassa province during the dry season, from 21 August to 4 October 2019. We observed water sources and conducted microbiological water quality tests and structured household interviews. Findings: We included 1313 households, of which 812 (61.8%) used water from an improved source. There was no significant difference in presence of total coliforms between water sampled at improved and unimproved water sources, 62.7% (509 samples) and 65.7% (329 samples), respectively (P-value = 0.267). Households using improved water sources spent significantly longer time collecting water (59.1 minutes; standard deviation, SD: 55.2) than households using unimproved sources (49.8 minutes; SD: 58.0; P-value < 0.001). A smaller proportion of households using improved sources had access to water sources available 24 hours per day than that of households using unimproved sources, 71.7% (582 households) versus 94.2% (472 households; P-value < 0.001). Of the 240 households treating water collected from improved sources, 204 (85.4%) had total coliforms in their water, while treated water from 77 of 107 (72.0%) households collecting water from an unimproved source were contaminated. Conclusion: Current access to an improved water source does not ensure microbiological safety of water and thereby using access as the proxy indicator for safe drinking and cooking water is questionable. Poor quality of water calls for the need for integration of water quality assessment into regular monitoring programmes.

What lies underneath: Precise classification of brain states using time-dependent topological structure of dynamics.

The self-organising global dynamics underlying brain states emerge from complex recursive nonlinear interactions between interconnected brain regions. Until now, most efforts of capturing the causal mechanistic generating principles have supposed underlying stationarity, being unable to describe the non-stationarity of brain dynamics, i.e. time-dependent changes. Here, we present a novel framework able to characterise brain states with high specificity, precisely by modelling the time-dependent dynamics. Through describing a topological structure associated to the brain state at each moment in time (its attractor or 'information structure'), we are able to classify different brain states by using the statistics across time of these structures hitherto hidden in the neuroimaging dynamics. Proving the strong potential of this framework, we were able to classify resting-state BOLD fMRI signals from two classes of post-comatose patients (minimally conscious state and unresponsive wakefulness syndrome) compared with healthy controls with very high precision.

Molecular characterization of diarrheagenic Escherichia coli isolates from children with diarrhea: A cross-sectional study in four provinces of Mozambique: Diarrheagenic Escherichia coli in Mozambique

Diarrheal disease is one of the major causes of childhood mortality in resource-limited countries (Vos et al., 2017). In 2019, diarrhea caused 499,950 deaths globally among children under 5 years old (Paulson et al., 2021); the highest number of deaths was in Africa (Abba et al., 2009; Vos et al., 2017...

Evaluation of the multidrug-resistant tuberculosis surveillance system in Maputo City, Mozambique in the period 2017-2018.

Introduction: multidrug-resistant tuberculosis (MDR-TB) remains a public health problem worldwide. In Mozambique, cases of MDR-TB have increased annually. In 2018, 1,206 cases were reported, as compared to 943 cases in 2017. The aim of this study was to assess the surveillance system for multidrug-resistant tuberculosis in Maputo City. Methods: an extract from the national database was considered for a cut-out of the City of Maputo in the period 2017-2018; the study was conducted per the guidelines of the Centers for Disease Control and Prevention, where the description of the system was carried out, and evaluation of the attributes. Each attribute was evaluated according to the established criteria and parameters. Results: the surveillance system is based on the collection of data in health centers. Four hundred and six cases of MDR-TB were notified, of which 56.8% (231/406) were male and 95.9% (386/406) were ≥15 years. The system was complex with 4 levels of information transmission. With regard to flexibility, there was no changing the variables in the database. Acceptability was good. The quality of the data was regular with discrepancy of data of 14.5%. The system was considered stable as there was no system interruption. Timeliness with case notification monthly. The system sensitivity was 72.9%, the positive predictive value (PPV) was 2.3% and regarding utility the system has fulfilled its objectives. Conclusion: the system was not flexible, the data quality was regular, had moderate sensitivity and low positive predictive value. Continuous assessment of data and scale up the diagnosis for the detection of cases of MDR-TB is recommended.

Evaluation of the Mozambique Antiretroviral Therapy (MozART) database as an antiretroviral therapy patient surveillance sys / Evaluation of the Mozambique Antiretroviral Therapy (MozART) database as an antiretroviral therapy patient surveillance sys

Mozambique antiretroviral therapy is a database used to monitor patients receiving antiretroviral treatment (ART). This study's objective was to evaluate the system for the purpose to monitor patients receiving ART. data from 287,052 patients who started ART from January to December 2017 were verified, and retention in care was assessed for 2018 in Mozambique. The Centers for Disease Control and Prevention guidelines for evaluating public health surveillance systems were used to conduct the evaluation. Simplicity, flexibility, data quality, representativeness and stability attributes were evaluated. a total of 93% (266,880/287,052) of patients on ART were adults ≥15 years old, and 65% (186,677/287,052) were female. The system was complex, it involved four organisations and its management was online. Data quality was moderate with 19% (1,533,885/8,037,456) of empty variable fields, 0.04% (123/287,052) observations with birth date later than the initial ART date, 0.2% (424/287,052) and 23% (68,039/287,052) with initial ART date and diagnosis date, later than the next ART pickup date. Nationally, 19%(31/161) of the districts did not have data in the information system. MozART cover health facilities with electronic patient tracking systems. Hence did not represent all patients on ART. While it was not possible to add variables of the electronic patient tracking, the system was stable as neither data or server interruptions were reported. the system was useful, stable, with moderate data quality, complex, not flexible and not representative. We recommend to health facilities and partners to develop and distribute procedures for data validation and completeness and report all patient tracking variables in the system.

Molecular characterization of diarrheagenic Escherichia coli isolates from children with diarrhea: A cross-sectional study in four provinces of Mozambique: Diarrheagenic Escherichia coli in Mozambique.

OBJECTIVES: Analyze the frequency of diarrheagenic Escherichia coli (DEC) pathotypes and their antimicrobial resistance profiles among children aged <15 years with diarrhea in four Mozambican provinces. METHODS: A cross-sectional hospital-based surveillance program of diarrhea was implemented in Maputo, Sofala, Zambézia, and Nampula. A single stool sample was collected from each child from May 2014 to May 2017. Culture methods and biochemical characterization were performed to detect E. coli strains. DEC pathotypes were determined by conventional polymerase chain reaction targeting specific virulence genes. Antimicrobial susceptibility was assessed by the Kirby-Bauer method. RESULTS: From 723 specimens analyzed by culture, 262 were positive for E. coli. A total of 208 samples were tested by polymerase chain reaction for DEC identification, of which 101 (48.6%) were positive for a DEC pathotype. The predominant pathotypes were enteroaggregative (66.3%, 67/101), enteropathogenic (15.8%, 16/101), enterotoxigenic (13.9%, 14/101), and enteroinvasive E. coli (4.0%, 4/101). No Shiga toxin-producing E. coli was identified. Regardless of the province, the most frequent pathotype was enteroaggregative E. coli. Isolated DEC presented high frequency of resistance to ampicillin (97.8%), tetracycline (68.3%), chloramphenicol (28.4%), nalidixic acid (19.5%), and gentamicin (14.4%). CONCLUSION: Children with diarrhea in Mozambique had DEC and higher resistance to ampicillin and tetracycline.

The seasonality of cholera in sub-Saharan Africa: a statistical modelling study.

BACKGROUND: Cholera remains a major threat in sub-Saharan Africa (SSA), where some of the highest case-fatality rates are reported. Knowing in what months and where cholera tends to occur across the continent could aid in improving efforts to eliminate cholera as a public health concern. However, largely due to the absence of unified large-scale datasets, no continent-wide estimates exist. In this study, we aimed to estimate cholera seasonality across SSA and explore the correlation between hydroclimatic variables and cholera seasonality. METHODS: Using the global cholera database of the Global Task Force on Cholera Control, we developed statistical models to synthesise data across spatial and temporal scales to infer the seasonality of excess (defined as incidence higher than the 2010-16 mean incidence rate) suspected cholera occurrence in SSA. We developed a Bayesian statistical model to infer the monthly risk of excess cholera at the first and second administrative levels. Seasonality patterns were then grouped into spatial clusters. Finally, we studied the association between seasonality estimates and hydroclimatic variables (mean monthly fraction of area flooded, mean monthly air temperature, and cumulative monthly precipitation). FINDINGS: 24 (71%) of the 34 countries studied had seasonal patterns of excess cholera risk, corresponding to approximately 86% of the SSA population. 12 (50%) of these 24 countries also had subnational differences in seasonality patterns, with strong differences in seasonality strength between regions. Seasonality patterns clustered into two macroregions (west Africa and the Sahel vs eastern and southern Africa), which were composed of subregional clusters with varying degrees of seasonality. Exploratory association analysis found most consistent and positive correlations between cholera seasonality and precipitation and, to a lesser extent, between cholera seasonality and temperature and flooding. INTERPRETATION: Widespread cholera seasonality in SSA offers opportunities for intervention planning. Further studies are needed to study the association between cholera and climate. FUNDING: US National Aeronautics and Space Administration Applied Sciences Program and the Bill & Melinda Gates Foundation.

Global structural stability and the role of cooperation in mutualistic systems.

Dynamical systems on graphs allow to describe multiple phenomena from different areas of Science. In particular, many complex systems in Ecology are studied by this approach. In this paper we analize the mathematical framework for the study of the structural stability of each stationary point, feasible or not, introducing a generalization for this concept, defined as Global Structural Stability. This approach would fit with the proper mathematical concept of structural stability, in which we find a full description of the complex dynamics on the phase space due to nonlinear dynamics. This fact can be analyzed as an informational field grounded in a global attractor whose structure can be completely characterized. These attractors are stable under perturbation and suppose the minimal structurally stable sets. We also study in detail, mathematically and computationally, the zones characterizing different levels of biodiversity in bipartite graphs describing mutualistic antagonistic systems of population dynamics. In particular, we investigate the dependence of the region of maximal biodiversity of a system on its connectivity matrix. On the other hand, as the network topology does not completely determine the robustness of the dynamics of a complex network, we study the correlation between structural stability and several graph measures. A systematic study on synthetic and biological graphs is presented, including 10 mutualistic networks of plants and seed-dispersal and 1000 random synthetic networks. We compare the role of centrality measures and modularity, concluding the importance of just cooperation strength among nodes when describing areas of maximal biodiversity. Indeed, we show that cooperation parameters are the central role for biodiversity while other measures act as secondary supporting functions.

Do Antiangiogenics Promote Clot Instability? Data from the TESEO Prospective Registry and Caravaggio Clinical Trial.

BACKGROUND: Venous thromboembolism (VTE) is a common complication in cancer patients. Much of its morbidity stems from the development of fatal pulmonary embolisms (PE). Little is known about the factors involved in clot stability, with angiogenesis possibly being implicated. METHODS: The database is from the TESEO prospective registry that recruits cancer patients with VTE from 41 Spanish hospitals. Independent validation was conducted in a cohort from the Caravaggio trial. The objective is to evaluate the association between exposure to antiangiogenic therapies and the PE/VTE proportion in oncological patients. RESULTS: In total, 1,536 subjects were evaluated; 58.4% (n = 894) had a PE and 7% (n = 108) received antiangiogenic therapy (bevacizumab in 75%). The PE/VTE proportion among antiangiogenic-treated individuals was 77/108 (71.3%) versus 817/1,428 (57.2%) among those receiving other alternative therapies (p = 0.004). The effect of the antiangiogenics on the PE/VTE proportion held up across all subgroups except for active smokers or those with chronic obstructive pulmonary disease. Exposure to antiangiogenics was associated with increased PEs, odds ratio (OR) 2.27 (95% CI, 1.42-3.63). In the Caravaggio trial, PE was present in 67% of the individuals treated with antiangiogenics, 50% of those who received chemotherapy without antiangiogenic treatment, and 60% without active therapy (p = 0.0016). CONCLUSION: Antiangiogenics are associated with increased proportion of PE in oncological patients with VTE. If an effect on clot stability is confirmed, the concept of thrombotic risk in cancer patients should be reconsidered in qualitative terms.

Immunogenicity of Reduced-Dose Monovalent Type 2 Oral Poliovirus Vaccine in Mocuba, Mozambique.

BACKGROUND: The monovalent type 2 oral poliovirus vaccine (mOPV2) stockpile is low. One potential strategy to stretch the existing mOPV2 supply is to administer a reduced dose: 1 drop instead of 2. METHODS: We conducted a randomized, controlled, open-label, noninferiority trial (10% margin) to compared immunogenicity after administration of 1 versus 2 drops of mOPV2. We enrolled 9-22-month-old infants from Mocuba district of Mozambique. Poliovirus neutralizing antibodies were measured in serum samples collected before and 1 month after mOPV2 administration. Immune response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) after vaccination or boosting titers by ≥4-fold for those with titers between 1:8 and 1:362 at baseline. The trial was registered at anzctr.org.au (no. ACTRN12619000184178p). RESULTS: We enrolled 378 children, and 262 (69%) completed per-protocol requirements. The immune response of mOPV2 was 53.6% (95% confidence interval, 44.9%-62.1%) and 60.6% (52.2%-68.4%) in 1-drop and 2-drop recipients, respectively. The noninferiority margin of the 10% was not reached (difference, 7.0%; 95% confidence interval, -5.0% to 19.0%). CONCLUSION: A small loss of immunogenicity of reduced mOPV2 was observed. Although the noninferiority target was not achieved, the Strategic Advisory Group of Experts on Immunization recommended the 1-drop strategy as a dose-sparing measure if mOPV2 supplies deteriorate further.