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1.
Virol J ; 18(1): 205, 2021 10 12.
Article in English | MEDLINE | ID: covidwho-1619949

ABSTRACT

Co-infections have a key role in virus transmission in wild reservoir hosts. We investigated the simultaneous presence of astroviruses, coronaviruses, and paramyxoviruses in bats from Madagascar, Mayotte, Mozambique, and Reunion Island. A total of 871 samples from 28 bat species representing 8 families were tested by polymerase chain reactions (PCRs) targeting the RNA-dependent RNA-polymerase genes. Overall, 2.4% of bats tested positive for the presence of at least two viruses, only on Madagascar and in Mozambique. Significant variation in the proportion of co-infections was detected among bat species, and some combinations of co-infection were more common than others. Our findings support that co-infections of the three targeted viruses occur in bats in the western Indian Ocean region, although further studies are needed to assess their epidemiological consequences.


Subject(s)
Astroviridae Infections/epidemiology , Chiroptera/virology , Coinfection/epidemiology , Coronavirus Infections/epidemiology , Paramyxoviridae Infections/epidemiology , Animals , Madagascar , Mozambique , Reunion
2.
PLoS Negl Trop Dis ; 15(12): e0010064, 2021 12.
Article in English | MEDLINE | ID: covidwho-1581898

ABSTRACT

BACKGROUND: Among the many collaterals of the COVID-19 pandemic is the disruption of health services and vital clinical research. COVID-19 has magnified the challenges faced in research and threatens to slow research for urgently needed therapeutics for Neglected Tropical Diseases (NTDs) and diseases affecting the most vulnerable populations. Here we explore the impact of the pandemic on a clinical trial for plague therapeutics and strategies that have been considered to ensure research efforts continue. METHODS: To understand the impact of the COVID-19 pandemic on the trial accrual rate, we documented changes in patterns of all-cause consultations that took place before and during the pandemic at health centres in two districts of the Amoron'I Mania region of Madagascar where the trial is underway. We also considered trends in plague reporting and other external factors that may have contributed to slow recruitment. RESULTS: During the pandemic, we found a 27% decrease in consultations at the referral hospital, compared to an 11% increase at peripheral health centres, as well as an overall drop during the months of lockdown. We also found a nation-wide trend towards reduced number of reported plague cases. DISCUSSION: COVID-19 outbreaks are unlikely to dissipate in the near future. Declining NTD case numbers recorded during the pandemic period should not be viewed in isolation or taken as a marker of things to come. It is vitally important that researchers are prepared for a rebound in cases and, most importantly, that research continues to avoid NTDs becoming even more neglected.


Subject(s)
COVID-19 , Health Impact Assessment , Neglected Diseases/drug therapy , Plague/drug therapy , Randomized Controlled Trials as Topic , Research , Tropical Medicine/trends , Disease Notification , Epidemiological Monitoring , Humans , Madagascar/epidemiology , Pandemics , Patient Acceptance of Health Care , Patient Selection , Plague/epidemiology , Referral and Consultation/trends
3.
Emerg Infect Dis ; 27(12): 3163-3165, 2021 12.
Article in English | MEDLINE | ID: covidwho-1528795

ABSTRACT

During the coronavirus disease pandemic, we observed a 6.4-fold increase in typhoid intestinal perforation incidence in Antananarivo, Madagascar. Thirteen perforations occurred within 6 months (February 2020-July 2020), compared with 13 perforations during the previous 41 months (August 2016-January 2020). The increase may be attributable to delayed healthcare seeking during the pandemic.


Subject(s)
COVID-19 , Intestinal Perforation , Typhoid Fever , Humans , Intestinal Perforation/epidemiology , Intestinal Perforation/etiology , Madagascar/epidemiology , SARS-CoV-2 , Typhoid Fever/epidemiology
6.
Molecules ; 26(18)2021 Sep 12.
Article in English | MEDLINE | ID: covidwho-1410349

ABSTRACT

Chemical and biological investigation of the Madagascar endemic plant Saldinia proboscidea led to the isolation of an isomer of artemisinin, (-)-6-epi-artemisinin (2). Its structure was elucidated using a combination of NMR and mass spectrometry. The absolute configuration was established by chemical syntheses of compound 2 as well as a new stereoisomer (3). The comparable bioactivities of artemisinin (1) and its isomer (-)-6-epi-artemisinin (2) revealed that this change in configuration was not critical to their biological properties. Bioactivity was assessed using an apoptosis induction assay, a SARS-CoV-2 inhibitor assay, and a haematin polymerization inhibitory activity (HPIA) assay. This is the first report of an artemisinin-related compound from a genus not belonging to Artemisia and it is the first isolation of an artemisinin-related natural product that is the opposite enantiomeric series relative to artemisinin from Artemisia annua.


Subject(s)
Antimalarials/chemistry , Artemisinins/chemistry , Plant Extracts/chemistry , Rubiaceae/chemistry , Madagascar , Stereoisomerism
7.
Front Public Health ; 9: 654299, 2021.
Article in English | MEDLINE | ID: covidwho-1348570

ABSTRACT

There are many outstanding questions about how to control the global COVID-19 pandemic. The information void has been especially stark in the World Health Organization Africa Region, which has low per capita reported cases, low testing rates, low access to therapeutic drugs, and has the longest wait for vaccines. As with all disease, the central challenge in responding to COVID-19 is that it requires integrating complex health systems that incorporate prevention, testing, front line health care, and reliable data to inform policies and their implementation within a relevant timeframe. It requires that the population can rely on the health system, and decision-makers can rely on the data. To understand the process and challenges of such an integrated response in an under-resourced rural African setting, we present the COVID-19 strategy in Ifanadiana District, where a partnership between Malagasy Ministry of Public Health (MoPH) and non-governmental organizations integrates prevention, diagnosis, surveillance, and treatment, in the context of a model health system. These efforts touch every level of the health system in the district-community, primary care centers, hospital-including the establishment of the only RT-PCR lab for SARS-CoV-2 testing outside of the capital. Starting in March of 2021, a second wave of COVID-19 occurred in Madagascar, but there remain fewer cases in Ifanadiana than for many other diseases (e.g., malaria). At the Ifanadiana District Hospital, there have been two deaths that are officially attributed to COVID-19. Here, we describe the main components and challenges of this integrated response, the broad epidemiological contours of the epidemic, and how complex data sources can be developed to address many questions of COVID-19 science. Because of data limitations, it still remains unclear how this epidemic will affect rural areas of Madagascar and other developing countries where health system utilization is relatively low and there is limited capacity to diagnose and treat COVID-19 patients. Widespread population based seroprevalence studies are being implemented in Ifanadiana to inform the COVID-19 response strategy as health systems must simultaneously manage perennial and endemic disease threats.


Subject(s)
COVID-19 , COVID-19 Testing , Humans , Madagascar/epidemiology , Pandemics , SARS-CoV-2 , Seroepidemiologic Studies
8.
EBioMedicine ; 68: 103419, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1258362

ABSTRACT

BACKGROUND: The incidence of the 2020 COVID-19 epidemic in Africa seems to be different from that of the rest of the world, however its true extent is probably underestimated. Conducting population based sero-surveys during the epidemic has moreover been extremely challenging, driving our group and others to study blood donor samples. METHODS: We collected regional epidemiological COVID-19 surveillance data, and simultaneously monitored anti-SARS-CoV-2 antibody seroprevalences monthly throughout the epidemic in 5 major Region-associated Blood Transfusion Centres of Madagascar over a period of 9 months. FINDINGS: Soon after attaining the first epidemic peaks between May and August 2020, both crude and population-weighted test-performance-adjusted seroprevalences of anti-SARS-CoV-2 antibodies was in Malagasy blood donors rapidly increased up to over 40% positivity. INTERPRETATION: These findings suggest a high cumulative incidence of infection and seroconversion, which may have contributed to the observed deceleration of infection rates, but was not sufficient to prevent the second epidemic wave that struck Madagascar in Spring 2021. FUNDING: This project was funded by the United States Agency for International Development.


Subject(s)
Antibodies, Viral/blood , Blood Donors , COVID-19/epidemiology , Epidemics , SARS-CoV-2/immunology , COVID-19/immunology , Female , Humans , Incidence , Madagascar/epidemiology , Male , Population Surveillance , Seroconversion , Seroepidemiologic Studies
9.
Science ; 372(6539)2021 04 16.
Article in English | MEDLINE | ID: covidwho-1201427

ABSTRACT

Animals in the wild are able to subsist on pathogen-infected and poisonous food and show immunity to various diseases. These may be due to their microbiota, yet we have a poor understanding of animal microbial diversity and function. We used metagenomics to analyze the gut microbiota of more than 180 species in the wild, covering diverse classes, feeding behaviors, geographies, and traits. Using de novo metagenome assembly, we constructed and functionally annotated a database of more than 5000 genomes, comprising 1209 bacterial species of which 75% are unknown. The microbial composition, diversity, and functional content exhibit associations with animal taxonomy, diet, activity, social structure, and life span. We identify the gut microbiota of wild animals as a largely untapped resource for the discovery of therapeutics and biotechnology applications.


Subject(s)
Animals, Wild/microbiology , Bacteria , Gastrointestinal Microbiome , Genome, Bacterial , Metagenome , Animals , Animals, Wild/classification , Animals, Wild/physiology , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Bacterial Toxins/metabolism , Behavior, Animal , Biodiversity , Databases, Nucleic Acid , Diet , Ecosystem , Falkland Islands , Feces/microbiology , Host Microbial Interactions , Israel , Madagascar , Metagenomics , Peptide Hydrolases/genetics , Peptide Hydrolases/metabolism , Phylogeny , Queensland , Uganda
10.
J Epidemiol Glob Health ; 10(4): 367-377, 2020 12.
Article in English | MEDLINE | ID: covidwho-1006610

ABSTRACT

The rapid detection of ongoing outbreak - and the identification of causative pathogen - is pivotal for the early recognition of public health threats. The emergence and re-emergence of infectious diseases are linked to several determinants, both human factors - such as population density, travel, and trade - and ecological factors - like climate change and agricultural practices. Several technologies are available for the rapid molecular identification of pathogens [e.g. real-time polymerase chain reaction (PCR)], and together with on line monitoring tools of infectious disease activity and behaviour, they contribute to the surveillance system for infectious diseases. Web-based surveillance tools, infectious diseases modelling and epidemic intelligence methods represent crucial components for timely outbreak detection and rapid risk assessment. The study aims to integrate the current prevention and control system with a prediction tool for infectious diseases, based on regression analysis, to support decision makers, health care workers, and first responders to quickly and properly recognise an outbreak. This study has the intention to develop an infectious disease regressive prediction tool working with an off-line database built with specific epidemiological parameters of a set of infectious diseases of high consequences. The tool has been developed as a first prototype of a software solution called Infectious Diseases Seeker (IDS) and it had been established in two main steps, the database building stage and the software implementation stage (MATLAB® environment). The IDS has been tested with the epidemiological data of three outbreaks occurred recently: severe acute respiratory syndrome epidemic in China (2002-2003), plague outbreak in Madagascar (2017) and the Ebola virus disease outbreak in the Democratic Republic of Congo (2018). The outcomes are promising and they reveal that the software has been able to recognize and characterize these outbreaks. The future perspective about this software regards the developing of that tool as a useful and user-friendly predictive tool appropriate for first responders, health care workers, and public health decision makers to help them in predicting, assessing and contrasting outbreaks.


Subject(s)
Communicable Diseases , Disease Outbreaks , Public Health Surveillance , Software , China/epidemiology , Communicable Diseases/epidemiology , Democratic Republic of the Congo/epidemiology , Female , Hemorrhagic Fever, Ebola/epidemiology , Humans , Madagascar/epidemiology , Male , Plague/epidemiology , Public Health Surveillance/methods , Severe Acute Respiratory Syndrome/epidemiology
11.
Trop Med Int Health ; 26(6): 621-631, 2021 06.
Article in English | MEDLINE | ID: covidwho-1119265

ABSTRACT

OBJECTIVES: Specific serological tests are mandatory for reliable SARS-CoV-2 diagnostics and seroprevalence studies. Here, we assess the specificities of four commercially available SARS-CoV-2 IgG ELISAs in serum/plasma panels originating from Africa, South America, and Europe. METHODS: 882 serum/plasma samples collected from symptom-free donors before the COVID-19 pandemic in three African countries (Ghana, Madagascar, Nigeria), Colombia, and Germany were analysed with three nucleocapsid-based ELISAs (Euroimmun Anti-SARS-CoV-2-NCP IgG, EDI™ Novel Coronavirus COVID-19 IgG, Mikrogen recomWell SARS-CoV-2 IgG), one spike/S1-based ELISA (Euroimmun Anti-SARS-CoV-2 IgG), and in-house common cold CoV ELISAs. RESULTS: High specificity was confirmed for all SARS-CoV-2 IgG ELISAs for Madagascan (93.4-99.4%), Colombian (97.8-100.0%), and German (95.9-100.0%) samples. In contrast, specificity was much lower for the Ghanaian and Nigerian serum panels (Ghana: NCP-based assays 77.7-89.7%, spike/S1-based assay 94.3%; Nigeria: NCP-based assays 39.3-82.7%, spike/S1-based assay 90.7%). 15 of 600 African sera were concordantly classified as positive in both the NCP-based and the spike/S1-based Euroimmun ELISA, but did not inhibit spike/ACE2 binding in a surrogate virus neutralisation test. IgG antibodies elicited by previous infections with common cold CoVs were found in all sample panels, including those from Madagascar, Colombia, and Germany and thus do not inevitably hamper assay specificity. Nevertheless, high levels of IgG antibodies interacting with OC43 NCP were found in all 15 SARS-CoV-2 NCP/spike/S1 ELISA positive sera. CONCLUSIONS: Depending on the chosen antigen and assay protocol, SARS-CoV-2 IgG ELISA specificity may be significantly reduced in certain populations probably due to interference of immune responses to endemic pathogens like other viruses or parasites.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Immunoglobulin G/blood , Adolescent , Adult , COVID-19/virology , Child , Child, Preschool , Colombia , Coronavirus Nucleocapsid Proteins/immunology , Female , Germany , Ghana , Humans , Madagascar , Male , Middle Aged , Nigeria , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology , Young Adult
12.
Influenza Other Respir Viruses ; 15(4): 457-468, 2021 07.
Article in English | MEDLINE | ID: covidwho-1083542

ABSTRACT

BACKGROUND: Following the first detection of SARS-CoV-2 in passengers arriving from Europe on 19 March 2020, Madagascar took several mitigation measures to limit the spread of the virus in the country. METHODS: Nasopharyngeal and/or oropharyngeal swabs were collected from travellers to Madagascar, suspected SARS-CoV-2 cases and contact of confirmed cases. Swabs were tested at the national reference laboratory using real-time RT-PCR. Data collected from patients were entered in an electronic database for subsequent statistical analysis. All distribution of laboratory-confirmed cases were mapped, and six genomes of viruses were fully sequenced. RESULTS: Overall, 26,415 individuals were tested for SARS-CoV-2 between 18 March and 18 September 2020, of whom 21.0% (5,553/26,145) returned positive. Among laboratory-confirmed SARS-CoV-2-positive patients, the median age was 39 years (IQR: 28-52), and 56.6% (3,311/5,553) were asymptomatic at the time of sampling. The probability of testing positive increased with age with the highest adjusted odds ratio of 2.2 [95% CI: 1.9-2.5] for individuals aged 49 years and more. Viral strains sequenced belong to clades 19A, 20A and 20B indicative of several independent introduction of viruses. CONCLUSIONS: Our study describes the first wave of the COVID-19 in Madagascar. Despite early strategies in place Madagascar could not avoid the introduction and spread of the virus. More studies are needed to estimate the true burden of disease and make public health recommendations for a better preparation to another wave.


Subject(s)
COVID-19/epidemiology , Adult , Asymptomatic Infections/epidemiology , COVID-19/diagnosis , COVID-19/transmission , COVID-19 Nucleic Acid Testing , Epidemiological Monitoring , Female , Genome, Viral/genetics , Humans , Madagascar/epidemiology , Male , Middle Aged , Nasopharynx/virology , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Travel
15.
Infect Genet Evol ; 87: 104668, 2021 01.
Article in English | MEDLINE | ID: covidwho-963228

ABSTRACT

We scrutinize the evolution of COVID-19 in Madagascar by comparing results from three approaches (cubic polynomial, semi-gaussian and gaussian-like models) which we use to provide an analytical form of the spread of the pandemic. In so doing, we introduce (for the first time) the ratio ℜI/Tc,d of the cumulative and daily numbers of infected persons over the corresponding one of tests which are expected to be less sensitive to the number of the tests because the credibility of the results based only on the absolute numbers often raises some criticisms. We also give and compare the effective reproduction number Reff from different approaches and with the ones of some European countries with a small number of population (Greece, Switzerland) and some other African countries. Finally, we show and comment the evolution of the total number of deaths and of the per cent number of cured persons and discuss the performance of the medical care.


Subject(s)
COVID-19/epidemiology , Models, Statistical , COVID-19/transmission , COVID-19/virology , Humans , Madagascar/epidemiology , Pandemics , SARS-CoV-2/isolation & purification
16.
Int J Infect Dis ; 103: 338-342, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-943190

ABSTRACT

OBJECTIVES: Quantitative estimates of the impact of infectious disease outbreaks are required to develop measured policy responses. In many low- and middle-income countries, inadequate surveillance and incompleteness of death registration are important barriers. DESIGN: Here, we characterize how large an impact on mortality would have to be for being detectable using the uniquely detailed mortality notification data from the city of Antananarivo, Madagascar, with application to a recent measles outbreak. RESULTS: The weekly mortality rate of children during the 2018-2019 measles outbreak was 161% above the expected value at its peak, and the signal can be detected earlier in children than in the general population. This approach to detect anomalies from expected baseline mortality allows us to delineate the prevalence of COVID-19 at which excess mortality would be detectable with the existing death notification system in Antananarivo. CONCLUSIONS: Given current age-specific estimates of the COVID-19 fatality ratio and the age structure of the population in Antananarivo, we estimate that as few as 11 deaths per week in the 60-70 years age group (corresponding to an infection rate of approximately 1%) would detectably exceed the baseline. Data from 2020 will undergo necessary processing and quality control in the coming months. Our results provide a baseline for interpreting this information.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Limit of Detection , Madagascar/epidemiology , Measles/epidemiology , Measles/mortality , Middle Aged , Prevalence , SARS-CoV-2 , Young Adult
17.
Glob Health Action ; 13(1): 1816044, 2020 12 31.
Article in English | MEDLINE | ID: covidwho-814069

ABSTRACT

COVID-19 has wreaked havoc globally with particular concerns for sub-Saharan Africa (SSA), where models suggest that the majority of the population will become infected. Conventional wisdom suggests that the continent will bear a higher burden of COVID-19 for the same reasons it suffers from other infectious diseases: ecology, socio-economic conditions, lack of water and sanitation infrastructure, and weak health systems. However, so far SSA has reported lower incidence and fatalities compared to the predictions of standard models and the experience of other regions of the world. There are three leading explanations, each with different implications for the final epidemic burden: (1) low case detection, (2) differences in epidemiology (e.g. low R 0 ), and (3) policy interventions. The low number of cases have led some SSA governments to relaxing these policy interventions. Will this result in a resurgence of cases? To understand how to interpret the lower-than-expected COVID-19 case data in Madagascar, we use a simple age-structured model to explore each of these explanations and predict the epidemic impact associated with them. We show that the incidence of COVID-19 cases as of July 2020 can be explained by any combination of the late introduction of first imported cases, early implementation of non-pharmaceutical interventions (NPIs), and low case detection rates. We then re-evaluate these findings in the context of the COVID-19 epidemic in Madagascar through August 2020. This analysis reinforces that Madagascar, along with other countries in SSA, remains at risk of a growing health crisis. If NPIs remain enforced, up to 50,000 lives may be saved. Even with NPIs, without vaccines and new therapies, COVID-19 could infect up to 30% of the population, making it the largest public health threat in Madagascar for the coming year, hence the importance of clinical trials and continually improving access to healthcare.


Subject(s)
Coronavirus Infections/epidemiology , Models, Theoretical , Pneumonia, Viral/epidemiology , Africa South of the Sahara/epidemiology , COVID-19 , Humans , Incidence , Madagascar/epidemiology , Pandemics
18.
PLoS Negl Trop Dis ; 14(8): e0008251, 2020 08.
Article in English | MEDLINE | ID: covidwho-788854

ABSTRACT

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague's resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a "One Health" approach.


Subject(s)
Neglected Diseases/prevention & control , Plague/prevention & control , Yersinia pestis , Animals , Disease Outbreaks/prevention & control , Disease Reservoirs/microbiology , Humans , Insect Vectors , Madagascar/epidemiology , Neglected Diseases/epidemiology , Plague/epidemiology , Plague/transmission , Rodentia , Siphonaptera
19.
Infect Genet Evol ; 85: 104506, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-723000

ABSTRACT

Using the officially published data and aware of the uncertain source and insufficient number of samples, we present a first and (for the moment) unique attempt to study the first two months spread of the pandemic COVID-19 in Madagascar. The approach has been tested by predicting the number of contaminated persons for the next week after fitting the inputs data collected within 7 or 15 days using standard least χ2-fit method. Encouraged by this first test, we study systematically during 67 days, 1-2 weeks new data and predict the contaminated persons for the coming week. We find that the first month data are well described by a linear or quadratic polynomial with an increase of about (4-5) infected persons per day. Pursuing the analysis, one note that data until 46 days favours a cubic polynomial behaviour which signals an eventual near future stronger growth as confirmed by the new data on the 48th day. We complete the analysis until 67 days and find that the data until 77 days confirm the cubic polynomial behaviour which is a remarkable feature of the pandemic spread in Madagascar. We expect that these results will be useful for some new model buildings. A comparison with some other SI-like models predictions is done. These results for infected persons may also be interpreted as the lowest values of the real cases due to the insufficient number of samples (about 12,907 for 27 million habitants on 05/06/20). The data analysis of the absolute number of cured persons until 67 days shows an approximate linear behaviour with about 3 cured persons per day. However, the number of percentage number of cured persons decreases above 42-46 days indicating the limits of the hospital equipment and care to face the 2nd phase of the pandemic for the 67th first days. Some comments on the social, economical and political impacts of COVID-19 and confinement for Madagascar and, in general, for Worldwide are shortly discussed.


Subject(s)
COVID-19/epidemiology , Algorithms , Humans , Madagascar/epidemiology , Models, Statistical
20.
Science ; 367(6483): 1178, 2020 03 13.
Article in English | MEDLINE | ID: covidwho-124609
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