Assessment of surveillance predictors for suspected respiratory syncytial virus, influenza and Streptococcus pneumoniae infections in children aged <5 years in Madagascar.

Background: The lack of rapid, sensitive and affordable diagnostic tests that can distinguish a wide variety of respiratory pathogens at the point of care is an obstacle to the rapid implementation of control measures following events and epidemics. In addition, the absence of a standardized case definition to differentiate putative aetiologies is a challenge to assessing the burden of disease. This study aimed to identify the clinical spectrum of respiratory pathogens commonly associated with respiratory tract infections in the context of disease surveillance. Methods: Data obtained from prospective hospital-based severe acute respiratory infection surveillance among children aged <5 years from November 2010 to July 2013 were used in this study. Results: Intercostal recession and dyspnoea were predictive of respiratory syncytial virus (RSV) infection, whereas headache and chills were more often observed during influenza A infection. Male patients were at a higher risk for RSV infection than female patients. Productive cough, chills, sweating and weight loss were significantly associated with Streptococcus pneumoniae infection. The presence of fever did not necessarily indicate RSV infection. Conclusions: Combined with other examinations, this study shows the value of including the syndromic approach in the panel of diagnostic criteria for rapid identification of the risk of infectious diseases in areas where laboratory diagnostics are challenging. Given the current situation with coronavirus disease 2019, this approach may help decision makers to implement appropriate control measures.

Genome-based insights into the resistomes and mobilomes of two Providencia rettgeri strains isolated from wound infections in Madagascar.

OBJECTIVES: A molecular analysis was performed of two Providencia rettgeri (P. rettgeri) strains (Pr 297 and Pr 269) collected in 2007 and 2009 from wound swabs of patients admitted to the intensive care units at Joseph Ravoangy Andrianavalona hospital and the Military Hospital in Antananarivo, Madagascar. METHODS: The two P. rettgeri isolates were subjected to susceptibility testing. Whole genome sequencing was performed to characterise the antibiotic resistance genes, genomic islands and mobilomes (integrons, plasmids and insertion sequences). RESULTS: All isolates were found to be multidrug-resistant. Antibiotic-resistant genes described were amongst eight different classes of antimicrobial agents. Thirty insertion sequences and twelve genomic islands were predicted in each genome. Class 1 and class 2 integrons were found in both genomes, with gene cassette regions encompassing arr-2 - cmlA5 - blaOXA-10 - ant (3")-Ia and dfrA1 - sat2 - ant (3")-Ia - orfX, respectively. IncA/C2, ColM and ColE1-like plasmids were described harbouring blaCMY-30, qnrD and aac(6')-Ib-cr4 genes, respectively. Phylogenetic analysis showed that Pr 297 and Pr 269 isolates were genetically identical and clustered with P. rettgeri strains described in the USA and Spain. CONCLUSIONS: It is believed that this is the first molecular characterisation of wound infection pathogens from Madagascan patients and the first description of P. rettgeri co-producing CMY-30, OXA-10 and AAC(6')-Ib-cr4 enzymes. The diversity of the resistance determinants and mobile genetic elements was probably due to extensive horizontal gene transfer events, highlighting the need to conduct further molecular monitoring studies to understand the genomic plasticity of resistant bacteria in Madagascan hospitals.

Epidemiology of severe acute respiratory infections from hospital-based surveillance in Madagascar, November 2010 to July 2013.

BACKGROUND: Few comprehensive data exist regarding the epidemiology of severe acute respiratory infections (SARI) in low income countries. This study aimed at identifying etiologies and describing clinical features of SARI-associated hospitalization in Madagascar. METHODS: It is a prospective surveillance of SARI in 2 hospitals for 3 years. Nasopharyngeal swabs, sputum, and blood were collected from SARI patients enrolled and tested for viruses and bacteria. Epidemiological and clinical information were obtained from case report forms. RESULTS: Overall, 876 patients were enrolled in the study, of which 83.1% (728/876) were tested positive for at least one pathogen. Viral and bacterial infections occurred in 76.1% (667/876) and 35.8% (314/876) of tested samples, respectively. Among all detected viruses, respiratory syncytial virus (RSV) was the most common (37.7%; 348/924) followed by influenza virus A (FLUA, 18.4%; 170/924), rhinovirus (RV, 13.5%; 125/924), and adenovirus (ADV, 8.3%; 77/924). Among bacteria, Streptococcus pneumoniae (S. pneumoniae, 50.3%, 189/370) was the most detected followed by Haemophilus influenzae type b (Hib, 21.4%; 79/370), and Klebsiella (4.6%; 17/370). Other Streptococcus species were found in 8.1% (30/370) of samples. Compared to patients aged less than 5 years, older age groups were significantly less infected with RSV. On the other hand, patients aged more than 64 years (OR = 3.66) were at higher risk to be infected with FLUA, while those aged 15-29 years (OR = 3.22) and 30-64 years (OR = 2.39) were more likely to be infected with FLUB (influenza virus B). CONCLUSION: The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. Amongst young children, the demonstrated burden of RSV should guide clinicians for a better case management of children. These findings reveal the need to develop point-of-care tests to avoid overuse of antibiotics and to promote vaccine that could reduce drastically the RSV hospitalizations.

Outcome risk factors during respiratory infections in a paediatric ward in Antananarivo, Madagascar 2010-2012.

BACKGROUND: Acute respiratory infections are a leading cause of infectious disease-related morbidity, hospitalisation and mortality among children worldwide, and particularly in developing countries. In these low-income countries, most patients with acute respiratory infection (ARI), whether it is mild or severe, are still treated empirically. The aim of the study was to evaluate the risk factors associated with the evolution and outcome of respiratory illnesses in patients aged under 5 years old. MATERIALS AND METHODS: We conducted a prospective study in a paediatric ward in Antananarivo from November 2010 to July 2012 including patients under 5 years old suffering from respiratory infections. We collected demographic, socio-economic, clinical and epidemiological data, and samples for laboratory analysis. Deaths, rapid progression to respiratory distress during hospitalisation, and hospitalisation for more than 10 days were considered as severe outcomes. We used multivariate analysis to study the effects of co-infections. RESULTS: From November 2010 to July 2012, a total of 290 patients were enrolled. Co-infection was found in 192 patients (70%). Co-infections were more frequent in children under 36 months, with a significant difference for the 19-24 month-old group (OR: 8.0). Sixty-nine percent (230/290) of the patients recovered fully and without any severe outcome during hospitalisation; the outcome was scored as severe for 60 children and nine patients (3%) died. Risk factors significantly associated with worsening evolution during hospitalisation (severe outcome) were admission at age under 6 months (OR = 5.3), comorbidity (OR = 4.6) and low household income (OR = 4.1). CONCLUSION: Co-mordidity, low-income and age under 6 months increase the risk of severe outcome for children infected by numerous respiratory pathogens. These results highlight the need for implementation of targeted public health policy to reduce the contribution of respiratory diseases to childhood morbidity and mortality in low income countries.

Case-control study of the etiology of infant diarrheal disease in 14 districts in Madagascar.

BACKGROUND: Acute diarrhea is a major cause of childhood morbidity and mortality worldwide. Its microbiological causes and clinico-epidemiological aspects were examined during the rainy seasons from 2008 to 2009 in 14 districts in Madagascar. METHODS: Stool specimens of 2196 children with acute diarrhea and 496 healthy children were collected in a community setting. Intestinal parasites were diagnosed by microscopy and bacteria by culturing methods. Rota-, astro and adenoviruses were identified using commercially available ELISA kits and rotaviruses were confirmed using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Intestinal microorganisms were isolated from 54.6% of diarrheal patients and 45.9% of healthy subjects (p = <0.01). The most common pathogens in diarrheic patients were intestinal parasites (36.5%). Campylobacter spp. and Rotavirus were detected in 9.7% and 6.7% of diarrheic patients. The detection rates of Entamoeba histolytica, Trichomonas intestinalis and Giardia lamblia were much greater in diarrheal patients than in non diarrheal subjects (odds ratios of 5.1, 3.2, 1.7 respectively). The abundance of other enteropathogens among the non diarrheal group may indicate prolonged excretion or limited pathogenicity. CONCLUSION: In developing countries, where the lack of laboratory capacities is great, cross sectional studies of enteropathogens and their spatial distribution, including diarrheal and non diarrheal subjects, are interesting tools in order to advise regional policies on treatment and diarrheic patient management.

Evaluation of four rapid immunochromatographic tests for the detection of cardiac troponin I.

Cardiac troponin I (cTnI) is a sensitive and specific marker of acute coronary syndromes and myocardial damage. During the past few years, it has become the preferred biochemical marker of myocardial infarction. However, due to the sensitivity required for its detection, only automated systems can be used in developed countries. However, these are rather expensive and unaffordable for most laboratories in developing countries. Many manufacturers have therefore proposed rapid immunochromatographic tests to detect cTnI. The aim of this study was to assess the limit of detection (LOD) and performance of four rapid immunochromatographic tests available in Madagascar. The four tests evaluated were Hexagon Troponin, Nadal troponin I cassette, Troponitest+, and Amicheck-Trop. Amicheck-Trop had a sensitivity and negative predictive value of about 80%, whereas for the three others, they were about 20%. The specificity of Amicheck-Trop of 87.3% was lower than the specificities of the other tests (98% to 100%). These differences were explained by the limits of detection of the tests: 0.3 to 0.4 ng/ml for Amicheck-Trop but only 1.8 to 2 ng/ml for the three other tests. It was concluded that Amicheck-Trop could be useful in the management of acute myocardial infarction or myocarditis in sparsely equipped laboratories in developing countries.

Dissemination of multidrug resistant Acinetobacter baumannii in various hospitals of Antananarivo Madagascar.

This study reports the dissemination of multidrug-resistant (MDR) OXA-23-producing Acinetobacter baumannii clones in hospitals in Antananarivo, Madagascar. A total of 53 carbapenem-resistant A. baumannii isolates were obtained from September 2006 to March 2009 in five hospitals. These resistant strains represent 44% of all A. baumannii isolates. The double disk synergy test was performed to screen for production of metallo-beta-lactamases. Polymerase chain reaction (PCR) and DNA sequencing were performed for the detection of bla(AmpC), bla(OXA-51),bla(OXA-23), bla(OXA-24), bla(IMP), bla(VIM). The presence of the insertion sequence ISAba1 relative to blaOXA-23 and blaOXA-51 was assessed by PCR. Isolates were typed by Rep-PCR. All the isolates were MDR and produced the OXA-23 carbapenemase, which was confirmed by sequencing. PCR analysis for AmpC and OXA-51 gave positive results for all strains studied. No isolates produced metallo-beta-lactamases. In all isolates ISAba1 laid upstream of blaOXA-23. The A. baumannii isolates were separated into two genotypes; genotype A had a higher prevalence (41 strains) than genotype B (12 strains). Genotype A was present in four hospitals, whilst genotype B had spread in two hospitals. The high frequency of MDR OXA-23-producing A. baumannii in various hospitals in Antananarivo is curious since carbapenems are not available in Madagascar, but it emphasises the need for infection control procedures and strict adherence to them to prevent the spread of these resistant organisms in Antananarivo and also the need to control the use of carbapenems in the future.