Clinical Survey of Dengue Virus Circulation in the Republic of Djibouti between 2011 and 2014 Identifies Serotype 3 Epidemic and Recommends Clinical Diagnosis Guidelines for Resource Limited Settings.

Dengue virus is endemic globally, throughout tropical and sub-tropical regions. While the number of epidemics due to the four DENV serotypes is pronounced in East Africa, the total number of cases reported in Africa (16 million infections) remained at low levels compared to Asia (70 million infections). The French Armed forces Health Service provides epidemiological surveillance support in the Republic of Djibouti through the Bouffard Military hospital. Between 2011 and 2014, clinical and biological data of suspected dengue syndromes were collected at the Bouffard Military hospital and analyzed to improve Dengue clinical diagnosis and evaluate its circulation in East Africa. Examining samples from patients that presented one or more Dengue-like symptoms the study evidenced 128 Dengue cases among 354 suspected cases (36.2% of the non-malarial Dengue-like syndromes). It also demonstrated the circulation of serotypes 1 and 2 and reports the first epidemic of serotype 3 infections in Djibouti which was found in all of the hospitalized patients in this study. Based on these results we have determined that screening for Malaria and the presence of the arthralgia, gastro-intestinal symptoms and lymphopenia < 1,000cell/ mm3 allows for negative predictive value and specificity of diagnosis in isolated areas superior to 80% up to day 6. This study also provides evidence for an epidemic of Dengue virus serotype 3 previously not detected in Djibouti.

High prevalence of multidrug resistant tuberculosis in Djibouti: a retrospective study.

INTRODUCTION: The Republic of Djibouti is an African country that exhibits one of the highest incidence rate of tuberculosis in the world. The aim of this study was to evaluate the prevalence of multidrug-resistant tuberculosis among new cases. METHODOLOGY: We studied retrospectively every tuberculosis case diagnosed over a 12-month period in patients hospitalized at the French Military Hospital of Bouffard. During this period, 1,274 samples from 675 patients were tested. RESULTS: We isolated 266 mycobacteria corresponding to 180 cases of tuberculosis. Thirty-three were fully susceptible and 57% met the tuberculosis criteria, with 46% primary resistance. No extensively-drug-resistant tuberculosis was found. CONCLUSION: Our results highlight a major concern about the situation in this part of the world.

Progenitor "Mycobacterium canettii" clone responsible for lymph node tuberculosis epidemic, Djibouti.

"Mycobacterium canettii," an opportunistic human pathogen living in an unknown environmental reservoir, is the progenitor species from which Mycobacterium tuberculosis emerged. Since its discovery in 1969, most of the ≈70 known M. canettii strains were isolated in the Republic of Djibouti, frequently from expatriate children and adults. We show here, by whole-genome sequencing, that most strains collected from February 2010 through March 2013, and associated with 2 outbreaks of lymph node tuberculosis in children, belong to a unique epidemic clone within M. canettii. Evolution of this clone, which has been recovered regularly since 1983, may mimic the birth of M. tuberculosis. Thus, recognizing this organism and identifying its reservoir are clinically important.

High Prevalence of Multidrug Resistant Tuberculosis in Djibouti: a Retrospective Study

Introduction:The Republic of Djibouti is an African country that exhibits one of the highest incidence rate of tuberculosis in the world. The aim of this study was to evaluate the prevalence of multidrug resistant tuberculosis among new cases. Methodology: We studied retrospectively every tuberculosis case diagnosed over a 12month period in patients hospitalized at the French military Hospital of Bouffard. During this period; 1;274 samples from 675 patients were tested. Results: We isolated 266 mycobacteria corresponding to 180 cases of tuberculosis. Thirty three were fully susceptible and 57 met the tuberculosis criteria; with 46 primary resistance. No extensively drug resistant tuberculosis was found. Conclusion: Our results highlight a major concern about the situation in this part of the world

Significance of the identification in the Horn of Africa of an exceptionally deep branching Mycobacterium tuberculosis clade.

Molecular and phylogeographic studies have led to the definition within the Mycobacterium tuberculosis complex (MTBC) of a number of geotypes and ecotypes showing a preferential geographic location or host preference. The MTBC is thought to have emerged in Africa, most likely the Horn of Africa, and to have spread worldwide with human migrations. Under this assumption, there is a possibility that unknown deep branching lineages are present in this region. We genotyped by spoligotyping and multiple locus variable number of tandem repeats (VNTR) analysis (MLVA) 435 MTBC isolates recovered from patients. Four hundred and eleven isolates were collected in the Republic of Djibouti over a 12 year period, with the other 24 isolates originating from neighbouring countries. All major M. tuberculosis lineages were identified, with only two M. africanum and one M. bovis isolates. Upon comparison with typing data of worldwide origin we observed that several isolates showed clustering characteristics compatible with new deep branching. Whole genome sequencing (WGS) of seven isolates and comparison with available WGS data from 38 genomes distributed in the different lineages confirms the identification of ancestral nodes for several clades and most importantly of one new lineage, here referred to as lineage 7. Investigation of specific deletions confirms the novelty of this lineage, and analysis of its precise phylogenetic position indicates that the other three superlineages constituting the MTBC emerged independently but within a relatively short timeframe from the Horn of Africa. The availability of such strains compared to the predominant lineages and sharing very ancient ancestry will open new avenues for identifying some of the genetic factors responsible for the success of the modern lineages. Additional deep branching lineages may be readily and efficiently identified by large-scale MLVA screening of isolates from sub-Saharan African countries followed by WGS analysis of a few selected isolates.

Thrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib.

BACKGROUND: Drugs targeting the VEGF pathway are associated with renal adverse events, including proteinuria, hypertension and thrombotic microangiopathy (TMA). Most cases of TMA are reported secondary to bevacizumab. It was shown recently that sunitinib, a small molecule inhibiting several tyrosine kinase receptors, including VEGF receptors, can also induce proteinuria, hypertension and biological features of TMA. Case. A 44-year-old woman with a history of malignant skin hidradenoma was started on sunitinib for refractory disease. She developed hypertension after 2 weeks and low-grade proteinuria after 4 weeks. Renal function remained normal, and biological signs of TMA were absent. A renal biopsy was performed 6 months later as proteinuria persisted, demonstrating typical features of TMA. The patient was given irbesartan, and sunitinib was continued for 3 months after diagnosis. Over this period, blood pressure and renal function remained stable and proteinuria became undetectable. CONCLUSION: We report on the first case of histologically documented TMA secondary to sunitinib and provide detailed description of renal histological involvement. This suggests that all anti-VEGF drugs may share a common risk for developing renal adverse events, including TMA. Our case highlights the possible discrepancy between mild clinical manifestation on one hand and severe TMA features on renal biopsy on the other hand and pleads for large indication of renal biopsy in this setting. The renin-angiotensin system blockers may be considered in patients with mild clinical manifestations and in the absence of therapeutic alternative to anti-VEGF drugs.

Epidemiological and phylogenetic evidence for patient-to-patient hepatitis C virus transmission during sclerotherapy of varicose veins.

The aim of this study was to provide evidence for patient-to-patient nosocomial hepatitis C virus (HCV) transmission during sclerotherapy of varicose veins. Forty-three patients who had evidence of current infection by genotype 2 HCV have had sclerotherapy by the same physician. Based on this observation, a detailed epidemiological questionnaire on risk factors for HCV in genotype 2 infected patients was conducted. Seventeen sequences in the hypervariable region 1 (HVR1) of the HCV genome obtained from 17 HCV RNA positive patients with a past history of sclerotherapy, were compared with 17 sequences derived from genotype 2 patients with no past history of sclerotherapy, and with 25 sequences sampled from GenBank. Two hundred seven genotype 2 HCV infected patients were included. The main risk factors for HCV infection were transfusion (n = 76), drug use (n = 6), and sclerotherapy of varicose veins (n = 62 including 43 (20.8%) by the same physician), other or unknown (n = 76). These sclerotherapy sessions were carried out in the 1980s for many years. Five of these 43 patients had jaundice within a few weeks after a sclerotherapy session. Sequence analysis of HVR1 from 17 patients who had sclerotherapy by the same physician revealed that they were all infected with HCV genotype 2c. The phylogenetic tree indicated clustering of the patients with a past history of sclerotherapy. The method by which infection was likely to have been transmitted was probably the use of a single vial for multiple patients. This study provides strong evidence that sclerotherapy of varicose veins is a risk factor for HCV infection.