Bayesian mapping of pulmonary tuberculosis in Antananarivo, Madagascar

<p>Abstract</p> <p>Background</p> <p>Tuberculosis (TB), an infectious disease caused by the <it>Mycobacterium tuberculosis </it>is endemic in Madagascar. The capital, Antananarivo is the most seriously affected area. TB had a non-random spatial distribution in this setting, with clustering in the poorer areas. The aim of this study was to explore this pattern further by a Bayesian approach, and to measure the associations between the spatial variation of TB risk and national control program indicators for all neighbourhoods.</p> <p>Methods</p> <p>Combination of a Bayesian approach and a generalized linear mixed model (GLMM) was developed to produce smooth risk maps of TB and to model relationships between TB new cases and national TB control program indicators. The TB new cases were collected from records of the 16 Tuberculosis Diagnostic and Treatment Centres (DTC) of the city from 2004 to 2006. And five TB indicators were considered in the analysis: number of cases undergoing retreatment, number of patients with treatment failure and those suffering relapse after the completion of treatment, number of households with more than one case, number of patients lost to follow-up, and proximity to a DTC.</p> <p>Results</p> <p>In Antananarivo, 43.23% of the neighbourhoods had a standardized incidence ratio (SIR) above 1, of which 19.28% with a TB risk significantly higher than the average. Identified high TB risk areas were clustered and the distribution of TB was found to be associated mainly with the number of patients lost to follow-up (SIR: 1.10, CI 95%: 1.02-1.19) and the number of households with more than one case (SIR: 1.13, CI 95%: 1.03-1.24).</p> <p>Conclusion</p> <p>The spatial pattern of TB in Antananarivo and the contribution of national control program indicators to this pattern highlight the importance of the data recorded in the TB registry and the use of spatial approaches for assessing the epidemiological situation for TB. Including these variables into the model increases the reproducibility, as these data are already available for individual DTCs. These findings may also be useful for guiding decisions related to disease control strategies.</p

Geographical and environmental approaches to urban malaria in Antananarivo (Madagascar)

<p>Abstract</p> <p>Background</p> <p>Previous studies, conducted in the urban of Antananarivo, showed low rate of confirmed malaria cases. We used a geographical and environmental approach to investigate the contribution of environmental factors to urban malaria in Antananarivo.</p> <p>Methods</p> <p>Remote sensing data were used to locate rice fields, which were considered to be the principal mosquito breeding sites. We carried out supervised classification by the maximum likelihood method. Entomological study allowed vector species determination from collected larval and adult mosquitoes. Mosquito infectivity was studied, to assess the risk of transmission, and the type of mosquito breeding site was determined. Epidemiological data were collected from November 2006 to December 2007, from public health centres, to determine malaria incidence. Polymerase chain reaction was carried out on dried blood spots from patients, to detect cases of malaria. Rapid diagnostic tests were used to confirm malaria cases among febrile school children in a school survey.</p> <p>A geographical information system was constructed for data integration. Altitude, temperature, rainfall, population density and rice field surface area were analysed and the effects of these factors on the occurrence of confirmed malaria cases were studied.</p> <p>Results</p> <p>Polymerase chain reaction confirmed malaria in 5.1% of the presumed cases. Entomological studies showed <it>An. arabiensis </it>as potential vector. Rice fields remained to be the principal breeding sites. Travel report was considered as related to the occurrence of <it>P. falciparum </it>malaria cases.</p> <p>Conclusion</p> <p>Geographical and environmental factors did not show direct relationship with malaria incidence but they seem ensuring suitability of vector development. Absence of relationship may be due to a lack of statistical power. Despite the presence of <it>An. arabiensis</it>, scarce parasitic reservoir and rapid access to health care do not constitute optimal conditions to a threatening malaria transmission. However, imported malaria case is suggestive to sustain the pocket transmission in Antananarivo.</p

Trials

After publication of the original article [1], the authors have notified us of an additional acknowledgement they wish to bring for their paper

Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models

Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions

Putative biomarkers of environmental enteric disease fail to correlate in a cross-sectional study in two study sites in Sub-Saharan Africa

Environmental enteric dysfunction (EED) is an elusive, inflammatory syndrome of the small intestine thought to be associated with enterocyte loss and gut leakiness and lead to stunted child growth. To date, the gold standard for diagnosis is small intestine biopsy followed by histology. Several putative biomarkers for EED have been proposed and are widely used in the field. Here, we assessed in a cross-sectional study of children aged 2-5 years for a large set of biomarkers including markers of protein exudation (duodenal and fecal alpha-1-antitrypsin (AAT)), inflammation (duodenal and fecal calprotectin, duodenal, fecal and blood immunoglobulins, blood cytokines, C-reactive protein (CRP)), gut permeability (endocab, lactulose-mannitol ratio), enterocyte mass (citrulline) and general nutritional status (branched-chain amino acids (BCAA), insulin-like growth factor) in a group of 804 children in two Sub-Saharan countries. We correlated these markers with each other and with anemia in stunted and non-stunted children. AAT and calprotectin, CRP and citrulline and citrulline and BCAA correlated with each other. Furthermore, BCAA, citrulline, ferritin, fecal calprotectin and CRP levels were correlated with hemoglobin levels. Our results show that while several of the biomarkers are associated with anemia, there is little correlation between the different biomarkers. Better biomarkers and a better definition of EED are thus urgently needed

Seroprevalence of malaria in inhabitants of the urban zone of Antananarivo, Madagascar

BACKGROUND: Antananarivo, the capital of Madagascar, is located at an altitude of over 1,200 m. The environment at this altitude is not particularly favourable to malaria transmission, but malaria nonetheless remains a major public health problem. The aim of this study was to evaluate exposure to malaria in the urban population of Antananarivo, by measuring the specific seroprevalence of Plasmodium falciparum. METHODS: Serological studies specific for P. falciparum were carried out with an indirect fluorescent antibody test (IFAT). In a representative population of Antananarivo, 1,059 healthy volunteers were interviewed and serum samples were taken. RESULTS: The seroprevalence of IgG+IgA+IgM was 56.1% and that of IgM was 5.9%. The major risk factor associated with a positive IgG+IgA+IgM IFAT was travel outside Antananarivo, whether in the central highlands or on the coast. The abundance of rice fields in certain urban districts was not associated with a higher seroprevalence. CONCLUSION: Malaria transmission levels are low in Antananarivo, but seroprevalence is high. Humans come into contact with the parasite primarily when travelling outside the city. Further studies are required to identify indigenous risk factors and intra-city variations more clearly

Viral Etiology of Influenza-Like Illnesses in Antananarivo, Madagascar, July 2008 to June 2009

In Madagascar, despite an influenza surveillance established since 1978, little is known about the etiology and prevalence of viruses other than influenza causing influenza-like illnesses (ILIs).From July 2008 to June 2009, we collected respiratory specimens from patients who presented ILIs symptoms in public and private clinics in Antananarivo (the capital city of Madagascar). ILIs were defined as body temperature ≥38°C and cough and at least two of the following symptoms: sore throat, rhinorrhea, headache and muscular pain, for a maximum duration of 3 days. We screened these specimens using five multiplex real time Reverse Transcription and/or Polymerase Chain Reaction assays for detection of 14 respiratory viruses. We detected respiratory viruses in 235/313 (75.1%) samples. Overall influenza virus A (27.3%) was the most common virus followed by rhinovirus (24.8%), RSV (21.2%), adenovirus (6.1%), coronavirus OC43 (6.1%), influenza virus B (3.9%), parainfluenza virus-3 (2.9%), and parainfluenza virus-1 (2.3%). Co-infections occurred in 29.4% (69/235) of infected patients and rhinovirus was the most detected virus (27.5%). Children under 5 years were more likely to have one or more detectable virus associated with their ILI. In this age group, compared to those ≥5 years, the risk of detecting more than one virus was higher (OR = 1.9), as was the risk of detecting of RSV (OR = 10.1) and adenovirus (OR = 4.7). While rhinovirus and adenovirus infections occurred year round, RSV, influenza virus A and coronavirus OC43 had defined period of circulation.In our study, we found that respiratory viruses play an important role in ILIs in the Malagasy community, particularly in children under 5 years old. These data provide a better understanding of the viral etiology of outpatients with ILI and describe for the first time importance of these viruses in different age group and their period of circulation

Human plague: An old scourge that needs new answers

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