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Bone strength in human cortical bone is determined by the composition and structure of both the mineral and collagen matrices and influenced by factors such as age, gender, health, lifestyle and genetic factors. Age-related changes in the bone matrix are known to result in loss of mechanical strength and increased fragility. In this study we show how Raman spectroscopy, with its exquisite sensitivity to the molecular structure of bone, reveals new insights into age- and sex-related differences. Raman analysis of 18 samples of cortical hip bone obtained from people aged between 47–82 years with osteoarthritis (OA) found subtle changes in the lipid and collagen secondary structure, and the carbonate (CO32−) and phosphate (PO43−) mineral ratios in the bone matrix. Significant differences were observed between older and younger bones, and between older female and older male bones; no significant differences were observed between younger male and female bones. Older female bones presented the lowest mineral to matrix ratios (MMR) and highest CO32−/PO43− ratios, and relative to lipid/collagen –CH2 deformation modes at 1450 cm−1 they had lowest overall mineral content, higher collagen cross linking and lipid content but lower levels of α-helix collagen structures than older male and younger male and female bones. These observations provided further insight on bone composition changes observed in the bone volume fraction (BV/TV) for the older female bones from microCT measurements on the same samples, while tissue mineral density (TMD) measurements had shown no significant differences between the samples.

Setting: Kinshasa, capital of Democratic Republic of Congo, has the high rate of multidrug resistant tuberculosis (MDR-TB) which is associated with poor treatment outcomes until 2013. A new approach was needed. Objectives: To implement a new strategy in order to improve treatment outcomes. Design: A retrospective cohort study reviewing all the patients diagnosed MDR Tuberculosis between 2014 and 2017. The study was conducted in the National Tuberculosis Program (NTP) framework comparing the short regimen and the WHO standard regimen. Results: From 1246 patients diagnosed RR/TB, 1073 were included in the analysis: 948 on shorter regimen, and 125 on WHO standard regimen. The strategy was based on patient-centered care. In the short regimen group, 62.7% were male, 61.4% were age 25 - 44 years, 52.6% had previous history of TB, 39.3% underweight, 12.5% HIV positive. The median time from diagnosis to treatment was 19 days (0 - 163). In the long regimen group, 75% were male, 37.6% were age 14 - 44 years, 61.6% underweight, 18.4% HIV positive. The median time from diagnosis to treatment was 19 days (0 - 114). Favorable outcomes represented 81.9% in the short regimen group versus 72% in the long regimen group. Death and loss to follow-up were more observed in long regimen group (27.2% versus 15.4%). Factors associated with unfavorable outcomes in the short regimen group included sex, age ≥ 45 years, previous TB history, HIV status, delay to begin treatment. For the long regimen, the factors age and delay emerged, underweight and HIV were borderline. Drug adverse events were reported respectively in 43.5% and 42.4% for short and long regimen; with gastrointestinal disturbances, vestibular troubles, ototoxicity, arthralgia and anemia as the most common in the 2 groups. Conclusion: The new approach improved favorable outcomes. Both short and long regimens reached a high level of favorable outcome compared to the previous study. The short regimen, well supervised seems to be superior to the long regimen in term of Death rate and loss to follow up (LTFU).

Background Steroid 21-hydroxylase deficiency is an autosomal recessive disorder, present in 90–95% of all cases with congenital adrenal hyperplasia (CAH). The classical simple virilizing (SV) form of the disease causes virilization of the external genitalia in newborn females and pseudo-precocious puberty in both sexes, due to reactive androgen overproduction. Case presentation We describe a 3.5-year-old girl presenting with pubarche, P2 according to Tanner, advanced bone age of 6 years and 10 months, and high serum levels of 17-hydroxyprogesterone (17-OHP). Molecular analysis of the nine most common pseudogene-derived CYP21A2 point mutations was performed in the patient and her family members using the polymerase chain reaction/amplification-created restriction site (PCR/ACRS) method. We detected the P30L/I172N genotype in the patient. She had inherited a mild P30L mutation from her mother and a severe I172N mutation from her father. Conclusions Although the CAH phenotype is determined by the allele that produces most of the enzyme activity and the mild non-classical (NC) phenotype should be expected, the mild P30L known to be more virilizing probably induced the classical SV phenotype in our patient. A continuous regimen of hydrocortisone at a recommended dose failed to decrease the 17-OHP sufficiently. Careful tapering of the dose did not help, and her pubic hair advanced to P3 according to Tanner. Individually tailored treatment is warranted in this patient.

Background Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. Methods of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. Results Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71). Conclusions Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes., In tuberculosis (TB) patients from post-conflict eastern Democratic Republic of the Congo, 11.1% had rifampicin-resistant TB, of whom 46.5% had no prior TB. Cures were achieved in 83% and 74% of patients on 9- and 20/24-month multidrug-resistant TB regimens, respectively.

The Democratic Republic of Congo is one of the countries with a high preva-lence of multidrug-resistant tuberculosis (MDR-TB) in Africa and worldwide. This study aims to describe the trends and level of screening since 2013. This is a retrospective descriptive study based on quarterly reports from the provinces. The number of cases, past histories, age, sex and HIV Co-infection was identi-fied. It emerges that the number of cases increases significantly but does not reach the forecasts yet (912 cases of MDR/RR and XDR diagnosed in 2017 out of 3948 cases expected with a gap of 77%). Patients with a history of TB pre-dominate (63.5% in 2017); but the proportion of patients with no history of TB increases (36.5% in 2017). This suggests high rates among contacts. Women (37.8%) and children under 15 (2.7%) are less represented. TB/HIV Co-infection is 12% as for sensitive cases. Efforts still need to be made to improve screening.

We reported recently that the elevated plus maze is a good tool for evaluating cognitive and motor functional changes in gamma-irradiated rats as a model for new drug evaluation and monitoring. The capacity of Garcinia kola to mitigate radiation-induced brain injury is currently unknown. We therefore assessed the effects of the neuroprotective medicinal plant Garcinia kola, on the cognitive and motor changes in this murine model of acute radiation syndrome. Wistar rats exposed once to an ionizing dose of Tc99m-generated Gamma radiation were treated with an ethyl acetate fraction of methanolic extract of Garcinia kola seeds (content of 100 mg/kg of extract) for 9 weeks. Cognitive and motor function indicators were assessed in the elevated plus maze in these animals and compared with irradiated control groups (vitamin C- and vehicle-treated groups) and the non-irradiated control rats. The irradiated control group displayed cachexia, shaggy and dirty fur, porphyrin deposits around eyes, decreased exploratory activity, reduced social interactions and a loss of thigmotaxis revealed by a marked decrease in rearing episodes and stretch attend posture episodes close to the walls of elevated plus maze closed arm, an increased central platform time, and decreases in open arm time and entries. This group further displayed a decrease in head dips and grooming episodes. Treatment with Garcinia kola, and in a lesser extent vitamin C, significantly prevented the body weight loss (P, The effects of G. kola (a medicinal plant in African traditional medicine) seed extract on the cognitive and motor changes in the murine model of acute radiation syndrome were assessed. The extract was found to mitigate body weight loss, cognitive and motor impairment in irradiated rats better than vitamin C., Graphical Abstract Graphical Abstract

Setting: Democratic Republic of the Congo is a high-burden TB country. Its capital, Kinshasa, reports annually about one-third of all MDR-TB cases in the country; thus, pre-XDRTB management is warranted. Objectives: To describe the main challenges in treating pre- XDR TB in this low resources setting and possible solutions. Method: This is a retrospective study of all pre-XDR TB patients diagnosed in Kinshasa in 2018. A personalized regimen was applied according to the clinical profile, drug availability, and the Drug susceptibility testing (DST). Treatment was administered by hospitalization during the intensive phase and in ambulatory care in the continuation phase except in emergencies. Monthly follow up included evaluating clinical and bacteriological features, renal and liver functions, QT interval on ECG, and audiometry for those under aminoglycosides. Results: Among the 236 MDR-TB patients identified in 2018, 14 had pre-XDR. Two died before treatment initiation. Of the remaining 12. 75% were male, 50% were aged 25–44 years, 66.7% had previous anti-tuberculosis treatment, 75% had a body mass index

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.)

Background Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)–detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). Methods We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. Results Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1–100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5–72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. Conclusions In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.

Andrographolide (1) a bitter, diterpenes lactone is the most biologically active constituent from Andrographis paniculata. Andrographolide showed in vitro inhibition of the growth of Ebola virus (Zaire) with EC50 activity of 10 µM which is twenty-five-fold the activity of the control Favipiravir (EC50 = 250µM) in the Crystal violet (Plaque reduction/ Neutral red (Toxicity) assay. It also showed significant activity against Dengue fever virus with EC50 value of 0.56 µg/ml in the Visual (Cytopathic effect/ Toxicity) Assay and EC50 of 0.58 µg/ml in the Neutral Red (Cytopathic effect/ Toxicity) Assay (comparable to the values obtained with 6-Azauridine as the positive control EC50 = 0.32 µg/ml and 0.38 µg/ml in the respective bioassays; and against SARS Coronavirus. Andrographolide had an EC50 of 1.2 µg/ml in the Visual (cytopathic effect/toxicity) assay and 1.1 µg/ml in the Neutral Red (cytopathic effect/toxicity) assay. The compound exerts several immunomodulatory properties. In experimental models, it effectively reduced the levels of proinflammatory cytokines such as IL-1/3, IL-6, GMCSF, and TNF-a. The compound has a good pharmacokinetics profile and relatively non-toxic even at high doses making it an experimental drug for the treatment of viral infections, with possible application in the control of the Novel Coronavirus, Covid – 19.

BackgroundExtensively drug-resistant tuberculosis (XDR TB) is a very serious form of tuberculosis that is burdened with a heavy mortality toll, especially before the advent of new TB drugs. The Democratic Republic of the Congo (DRC) is among the countries most affected by this new epidemic.MethodsA retrospective analysis was performed of the records of all patients with pre- and extensively drug-resistant tuberculosis hospitalized from January 1, 2015 to December 31, 2017 and monitored for at least 6 months to one year after the end of their treatment in Kinshasa; an individualized therapeutic regimen with bedaquiline for 20 months was built for each patient. The adverse effects were systematically monitored.ResultsOf the 40 laboratory-confirmed patients, 32 (80%) patients started treatment, including 29 preXRB and 3 XDR TB patients. In the eligible group, 3 patients (9.4%) had HIV-TB coinfections. The therapeutic success rate was 53.2%, and the mortality rate was 46.8% (15/32); there were no relapses, failures or losses to follow-up. All coinfected HIV-TB patients died during treatment. The cumulative patient survival rate was 62.5% at 3 months, 53.1% at 6 months and 53.1% at 20 months. The most common adverse events were vomiting, Skin rash, anemia and peripheral neuropathy.ConclusionThe new anti-tuberculosis drugs are a real hope for the management of Drug Resistant tuberculosis patient and other new therapeutic combinations may improve favorable outcomes.

Background Surveys conducted in 1991–1992 in the Mbam Valley (Cameroon) revealed that onchocerciasis was highly endemic, with community microfilarial loads (CMFL) > 100 microfilariae/snip in some villages. Also in 1991–1992, a survey of suspected cases of epilepsy (SCE) found 746 SCE using a questionnaire administered to individuals identified by key informants, with prevalences reaching 13.6% in some communities. From 1998, annual community-directed treatment with ivermectin (CDTI) was implemented to control onchocerciasis. In 2017, a door-to-door household survey was conducted in three of the villages visited in 1991–1992, using a standardized 5-item epilepsy screening questionnaire. Results In 2017, a total of 2286 individuals living in 324 households were screened (582 in Bayomen, 553 in Ngongol and 1151 in Nyamongo) and 112 SCE were identified (4.9%). Neurologists examined 92 of these SCE and confirmed the diagnosis of epilepsy for 81 of them (3.5%). Between the surveys in 1991–1992 and 2017, the prevalence of SCE decreased from 13.6% to 2.5% in Bayomen (P = 0.001), from 8.7% to 6.6% in Ngongol (P = 0.205) and from 6.4% to 5.4% in Nyamongo (P = 0.282). The median age of SCE shifted from 20 (IQR: 12–23) to 29 years (IQR: 18–33; P = 0.018) in Bayomen, from 16 (IQR: 12–21) to 26 years (IQR: 21–39; P

In this manuscript the authors have studied the first two patients who were successfully treated with the treatment regimen containing Bedaquiline as second-line drug. The patients were diagnosed with pre-extensively drug-resistant tuberculosis (preXDR TB) whose prognosis was fatal in Democratic Republic of Congo (DRC). Bedaquiline is arguably one of the molecules of the future in the management of ultra-resistant tuberculosis. However, a larger cohort study may help to establish its effectiveness. Case report: Patients 1, 29 years old, with a history of multidrug-resistant TB (MDR-TB) one year previously. He showed signs of TB impregnation again 6 months after the last treatment. Bascilloscopy was positive again. The pre-extensively tuberculosis (pre-XDR TB) diagnosis was made by the Hain test (GenoType® MTBDRsl, Hain Lifescience). Patient 2, brother of the first patient, with a history of MDR TB a year before. He had low back pain with right parietal dorso swelling four months after the last treatment. The x-ray of the column showed L4-L5 disc disease. Parietal ultrasound showed a parietal abscess to the right of thoracic vertebrae with fistulization. Surgical biopsy and pus culture confirmed the diagnosis of Pre-XDR Extrapulmonary TB. The treatment regimen was the same for both patients: 6 months with Amikacin (Am) Bedaquiline (Bdq) Prothionamide (Pto) Paraamino Salicylic acid (PAS) Linezolid (Lzd) Cycloserine (Cs) Pyrazinamide (Z) and 14 months with PAS Lzd Cs Z. The side effects were minor. Bacteriological controls (smears and cultures) after 20 months of treatment are negative to date.

International audience; BACKGROUND: The accurate detection of multidrug-resistant tuberculosis (MDR-TB) is critical for the application of appropriate patient treatment and prevention of transmission of drug-resistant Mycobacterium tuberculosis isolates. The goal of this study was to evaluate the correlation between phenotypic and molecular techniques for drug-resistant tuberculosis diagnostics. Molecular techniques used were the line probe assay genotype MTBDRplus and the recently described tuberculosis-spoligo-rifampin-isoniazid typing (TB-SPRINT) bead-based assay. Conventional drug susceptibility testing (DST) was done on a BACTECTM MGIT 960 TB. METHOD: We studied 80 M. tuberculosis complex (MTC) clinical isolates from Minas Gerais state, of which conventional DST had classified 60 isolates as MDR and 20 as drug susceptible. FINDINGS: Among the 60 MDR-TB isolates with MGIT as a reference, sensitivity, specificity, accuracy, and kappa for rifampicin (RIF) resistance using TB-SPRINT and MTBDRplus, were 96.7% versus 93.3%, 100.0% versus 100.0%, 97.5% versus 95.0% and 0.94 versus 0.88, respectively. Similarly, the sensitivity, specificity, accuracy, and kappa for isoniazid (INH) resistance were 85.0% and 83.3%, 100.0% and 100.0%, 88.8% and 87.5% and 0.74 and 0.71 for both tests, respectively. Finally, the sensitivity, specificity, accuracy, and kappa for MDR-TB were 85.0% and 83.3%, 100.0% and 100.0%, 88.8% and 87.5% and 0.74 and 0.71 for both tests, respectively. MAIN CONCLUSIONS: Both methods exhibited a good correlation with the conventional DST. We suggest estimating the cost-effectiveness of MTBDRplus and TB-SPRINT in Brazil.

Background Although disordered sleep patterns predispose to hypertension (HTN), little is known on the effect of the latter on sleep patterns in sub-Saharan Africa. This study therefore sought to generate preliminary data on the likelihood (risk) of Obstructive sleep apnea (OSA) in hypertensive patients, with the aid of sleep questionnaires. Methods This case–control study, age-and-sex-matched HTN patients with normotensive participants, and compared sleep patterns in either group determined with the aid of the Berlin Questionnaire (BQ) and Epworth Sleepiness Scale (ESS). Results Overall, 50 HTN and 54 age- and sex-matched normotensive participants were enrolled. The prevalence of snoring was higher in participants with hypertension compared to normotensives (58.0% versus 44.0% respectively), though not significantly, (p = 0.167). However, the hypertensive cases (aged on average 54.78 ± 8.79 years and with mean duration since diagnosis of 4.46 ± 4.36 years) had a significantly higher likelihood of Obstructive Sleep Apnea (OSA) than the controls (aOR = 5.03; 95% CI, 1.90–13.33, p = 0.001) and but no significant resulting daytime sleepiness (p = 0.421). There was no clear trend observed between both the risk of OSA and daytime sleepiness and HTN severity. Although not significant, participants with controlled hypertension had lower rates of risk of OSA compared to those with uncontrolled HTN (50.0% versus 63.2%, p = 0.718). Conclusions Preliminary findings of this study (the first of its kind in Cameroon) suggests that hypertension is positively associated with likelihood of OSA in Cameroon. Further studies are required to investigate this further and the role of sleep questionnaires in our setting, cheap and easy to use tools which can be used to identify early, patients with hypertension in need for further sleep investigations. This will contribute to improving their quality of life and adherence to anti-hypertension treatment.

Background: Tuberculosis remains a very common infectious disease in Democratic Republic of Congo (DRC). The resistance to drugs worsens the prognosis and the outcome of patients affected tuberculosis and increase their mortality. Objective: To identify factors associated with death among Multidrugs resistant tuberculosis (MDR/RR TB) patients referred to the referential hospital, Centre d’Excellence Damien (CEDA). Materials and Methods: A retrospective cohort study of patients attending health care to the Center CEDA, a referral center for management of MDR/RR-TB in DR Congo. This study included all MDR/RR-TB patients referred from February 1st, 2015 to February 29th, 2017. A multivariate COX regression was performed to identify factors associated with mortality in the target population. Kaplan Meier method described the survival of patients and the comparison of curves was performed by the test of log Rank. Results: 199 patients were included in our study. Male gender was predominant with a sex ratio of 1.3. The mean age of patients was 35.8 ± 13.9 years. Among them, 18 (15.1%) were died. The major complications were Chronicles pulmonary Heart failure (p = 0.035), Chronic respiratory insufficiency (p = 0.004), depression (p = 0.044), undernutrition (p = 0.033), alcohol addiction (p = 0.006) and high smoking (p = 0.019). In multivariated analysis, factors associated to the death were alcohol addiction (HRa = 12.64, 95% CI 2.36 - 14.55, p = 0.003), asthenia (HRa = 4.75, 95% CI 1.56 - 14.50, p < 0.001), pulmonary consolidation (HRa = 10.01 95% CI 2.34 - 12.86, p = 0.02), some chest X-ray abnormalities such as signs of pulmonary fibrosis (HR = 4.7, 95% CI 2.78 - 28.94, p = 0.002) and the Chronic respiratory insufficiency (HRa = 3.77, 95% CI 1.37 - 10.43, p = 0.010). Conclusion: The present retrospective cohort study revealed that structural and functional pulmonary alteration emerged as the main factors associated with mortality among MDR/RR TB patients in Kinshasa. National Tuberculosis Programs should take into account those parameters while defining mortality reduction strategy.

Epilepsy affects at least 50 million individuals worldwide, especially in sub-Saharan Africa (sSA). Cognitive impairment is common in people with epilepsy (PWE) yet, little is known on the burden of cognitive impairment in people with epilepsy in sSA. This study was thus designed to assess cognitive impairment in PWE or epilepsy-associated neurocognitive disorders (EAND) in a rural population in Cameroon.This was a case-control study including PWE and age/sex-matched healthy controls from July to September 2017 in Bilomo, a village in the Mbam and Kim Division. The Montreal Cognitive Assessment (MoCA), International HIV Dementia Scale (IHDS), Dubois' Five Word testing, Frontal Assessment Battery (FAB), Isaac's Set Test and the Clock drawing test were administered to the study participants to evaluate global and specific cognitive functions.Eighty participants were included (40 cases and 40 controls) with a mean age of 25.78 years. Using the MoCA, 87.5% of cases had cognitive impairment, against 37.5% of controls (p 0.001; OR 11.67; CI 3.40-45.09). Using the IHDS, the prevalence of global cognitive impairment was 84.6% among the cases against 40% for the controls (p = 0.001; OR 7.07; CI 2.29-29.19). Specifically, executive function deficits (92.5% of cases vs 40.0% of controls p = 0.001 OR = 18.50 CI; 4.48-105.08) and decreased verbal fluency (100% of cases against 45% of controls p 0.001) were the most affected cognitive domains. Longer duration of epilepsy and higher seizure frequency were associated with global cognitive impairment. Low level of education was associated with both decreased verbal fluency and executive dysfunction while a longer stay in Bilomo correlated with poor results on the Isaac's Set Test.The prevalence of cognitive impairment appears to be much higher in PWE in the Mbam valley, particularly decreased executive function and verbal fluency, than in people without epilepsy. Longer disease duration, higher seizure frequency, low level of education and length of stay in Bilomo are associated with poorer cognitive performance. More studies are needed to refine evaluation tools to better characterize and manage EAND in sSA.

The antidiabetic properties of extracts of three Nigerian medicinal plants - Ocimum basilicum L. (Lamiaceae, formerly Labiatae), Phyllanthus niruri L. (Euphorbiaceae) and Viscum album L. (Viscaceae or Loranthaceae) parasitic on Psidium guajava L. (Myrtaceae) on normoglycemic and alloxan-induced diabetic rats were studied. The extracts (258.3 g, 6.89% w/w of P. niruri, 189.17 g, 6.76% w/w of V. album and 131.50 g, 6.41% w/w of O. basilicum), obtained by 48 h cold maceration in methanol: methylene chloride (1:1), were evaluated for hypoglycemic and oral glucose tolerance effects in normoglycemic rats and antihyperglycemic effect in alloxan (100 mg/kg i.p) diabetic (blood glucose level ≥ 200 mg/dl) rats. The results showed that acute oral administration of the extracts to normoglycemic rats caused a mild to moderate non-dose-related reduction in blood glucose levels. The extracts significantly (P < 0.05) suppressed the acute postprandial rise in blood glucose to varying extents. Extract of O. basilicum lowered the elevated glucose level to 13.67% at 180 min while P. niruri and V. album reduced the glucose level to 16.87 and 17.33%, respectively. In alloxan diabetic rats, the extracts caused a significant (P < 0.05) non-dose-related reduction in blood glucose with 52.31 (O. basilicum), 44.29 (P. niruri) and 16.71% (V. album) maximum reduction at 6 h. Key words: Alloxan, diabetes mellitus, Nigerian medicinal plants.

Background: A high prevalence of epilepsy has been observed in several onchocerciasis-endemic countries, including Cameroon. However, little is known on the clinical presentations of the affected persons with epilepsy (PWE). A community-based study was conducted with the aim of describing the spectrum of seizures in selected onchocerciasis-endemic villages in Cameroon and documenting relevant medical history in patients with onchocerciasis-associated epilepsy (OAE). Methods: We carried out door-to-door surveys in 5 onchocerciasis-endemic villages in Cameroon and recruited all consenting PWE Epilepsy was diagnosed using a 2-step approach consisting of the administration of a standardized 5-item questionnaire followed by confirmation of the suspected cases by a neurologist. Onchocerciasis-associated epilepsy was defined as ?.2 seizures without an obvious cause, starting between the ages of 3-18 years in previously healthy persons having resided for at least 3 years in an onchocerciasis-endemic area. Ivermectin use by PWE was verified. Seizure history, relevant past medical, and family history, as well as neurological findings, were noted. Results: In all, 156 PWE were recruited in the 5 villages. The modal age group for epilepsy onset was 10-14 years. The diagnostic criteria for OAE were met by 93.2% of the PWE. Participants had one or more of the following seizure types: generalized tonic-conic seizures (89.1%), absences (38.5%), nodding (21.8%), focal nonmotor (7.7%), and focal motor seizures (1.9%). One case (0.6%) with the "Nakalanga syndrome" was identified. More than half (56.4%) of PWE had at least one seizure per month. In one village, 562% of PWE had onchocercal skin lesions. Conclusion: People with epilepsy in onchocerciasis-endemic villages in Cameroon present with a wide clinical spectrum including nodding seizures and Nakalanga features. A great majority of participants met the diagnostic criteria for OAE, suggesting that better onchocerciasis control could prevent new cases. Epilepsy management algorithms in these areas must be adjusted to reflect the varied seizure types. (C) 2018 Published by Elsevier Inc.

Several diagnostic tests are being developed to detect drug resistance in tuberculosis. In line with previous developments detecting rifampicin and isoniazid resistance using microbead-based systems (spoligoriftyping and TB-SPRINT), we present here an assay called TB-EFI detecting mutations involved in resistance to ethambutol, fluoroquinolones and the three classical injectable drugs (kanamycin, amikacin and capreomycin) in Mycobacterium tuberculosis. The proposed test includes both wild-type and mutant probes for each targeted locus. Basic analysis can be performed manually. An upgraded interpretation is made available in Excel 2016. Using a reference set of 61 DNA extracts, we show that TB-EFI provides perfect concordance with pyrosequencing. Concordance between genotypic resistance and phenotypic DST was relatively good (72 to 98% concordance), with lower efficiency for fluoroquinolones and ethambutol due to some untargeted mutations. When compared to phenotypical resistance, performances were similar to those obtained with Hain MTBDRs/assay, possibly thanks to the use of automatized processing of data although some mutations involved in fluoroquinolone resistance could not be included. When applied on three uncharacterized sets, phenotype could be predicted for 51% to 98% depending on the setting and the drug investigated, detecting one extensively drug-resistant isolate in each of a Pakistan and a Brazilian set of 91 samples, and 9 XDR among 43 multi-resistant Kazakhstan samples. By allowing high-throughput detection of second-line drugs resistance and of resistance to ethambutol that is often combined to second-line treatments, TB-EFI is a cost-effective assay for large-scale worldwide surveillance of resistant tuberculosis and XDR-TB control.

Background: A high epilepsy prevalence has been reported in several onchocerciasis-endemic villages along the Mbam and Sanaga river valleys in Cameroon, including Bilomo and Kelleng. We sought to determine the prevalence of epilepsy in these two villages following more than 13 years of community-directed treatment with ivermectin (CDTI). Methods: Door-to-door surveys were performed on the entire resident population in the villages in August 2017 and January 2018. Epilepsy was diagnosed using a 2-step approach: administration of a standardized 5-item questionnaire followed by confirmation by a neurologist. Previously published diagnostic criteria for onchocerciasis-associated epilepsy (OAE) were used. Ov16 serology was done for children aged 7-10 years to assess onchocerciasis transmission. Findings were compared with previous data from these two villages. Results: A total of 1525 individuals (1321 in Bilomo and 204 in Kelleng) in 233 households were surveyed in both villages. The crude prevalence of epilepsy was 4.6% in Bilomo (2017) and 7.8% in Kelleng (2018), including 12 (15.6% of cases) persons with epilepsy (PWE) with nodding seizures. The age and sex-standardized prevalence in Kelleng decreased from 13.5% in 2004 to 9.3% in 2018 (P < 0.001). The median age of PWE shifted from 17 (IQR: 12-22) years to 24 (IQR: 20-30) years in Bilomo (P < 0.001); and slightly from 24 (IQR: 14-34) years to 28 (IQR: 21.25-36.75) years in Kelleng (P = 0.112). Furthermore, 47.6% of all tested children between 7 and 10 years had Ov16 antibodies. Conclusions: There is a decrease in epilepsy prevalence after 13 years and more of CDTI in both villages. The age-shift observed in PWE suggests that ivermectin may prevent OAE in younger residents. Ov16 seropositivity in children indicates ongoing onchocerciasis transmission possibly due to suboptimal control measures. Our findings support the existence of OAE in Cameroon and highlight the need to strengthen onchocerciasis elimination programs., SCOPUS: ar.j, info:eu-repo/semantics/published

Objective:To summarize prevalence data on the neurologic complications of sickle cell disease (SCD) in Africa.Methods:We searched EMBASE, PubMed, and African Index Medicus to identify all relevant articles published from inception to May 31, 2016. Each study was reviewed for methodologic quality. A random-effects model was used to estimate the prevalence of neurologic complications of SCD across studies.Results:Thirty-one studies were included. Methodologic quality was high or moderate in 90% of studies. Stroke, conditional and abnormal cerebral blood flow, seizures, and headache were the complications most frequently reported, with overall prevalence rates of 4.2%, 10.6%, 6.1%, 4.4%, and 18.9%, respectively. Some complications, like silent brain infarcts, peripheral neuropathies, neurocognitive deficits, or moyamoya disease, have been rarely or not studied at all in the African setting. Incidence data were scarce and of poor quality.Conclusions:The burden of neurologic complications of SCD is important in Africa and most likely underestimated. A better evaluation of this burden requires larger prospective studies using standard up-to-date screening methods. Accessibility to diagnostic tools such as neuroimaging, transcranial Doppler, EEG, and neuropsychological evaluation, as well as to preventive and therapeutic interventions and trained health care providers, should be improved in routine clinical practice.

The independent effect of lipid lowering therapy (LLT) on venous thromboembolism (VTE) risk is uncertain.To test statin and non-statin LLT as potential VTE risk factors.Using Rochester Epidemiology Project resources, we identified all Olmsted County, MN residents with objectively diagnosed incident VTE (cases) over the 13-year period, 1988-2000 (n=1340), and one to two matched controls (n=1538). We reviewed their complete medical records for baseline characteristics previously identified as independent VTE risk factors, and for statin and non-statin LLT. Using conditional logistic regression, we tested the overall effect of LLT on VTE risk and also separately explored the role of statin versus that of non-statin LLT, adjusting for other baseline characteristics.Among cases and controls, 74 and 111 received statin LLT, and 32 and 50 received non-statin LLT, respectively. Univariately, and after individually controlling for other potential VTE risk factors (i.e., BMI, trauma/fracture, leg paresis, hospitalization for surgery or medical illness, nursing home residence, active cancer, central venous catheter, varicose veins, prior superficial vein thrombosis, diabetes, congestive heart failure, angina/myocardial infarction, stroke, peripheral vascular disease, smoking, anticoagulation), LLT was associated with decreased odds of VTE (unadjusted OR=0.73; p=0.03). When considered separately, statin and non-statin LLT were each associated with moderate, non-significant lower odds of VTE. After adjusting for angina/myocardial infarction, each was significantly associated with decreased odds of VTE (OR=0.63, p0.01 and OR=0.61, p=0.04, respectively).LLT is associated with decreased VTE risk after adjusting for known risk factors.

Optimal control of chronic hyperglycemia prevents both micro and macro vascular complications—a leading cause of morbidity and mortality in diabetic subjects. This study was undertaken to give credence to the traditional use of Newbouldia laevis leaves in the treatment of diabetes mellitus (DM). Dichloromethane-methanol (1:1) extract (DME) of N. laevis leaves was prepared by cold maceration. Separation of DME into column chromatographic fractions yielded the n-hexane fraction (HF), ethylacetate fraction (EF) and methanol fraction (MF). The extract and fractions were evaluated for antihyperglycemic activity in alloxanized diabetic rats. The results showed that the oral administration of extract and fractions (250, 500, 1000 mg/kg) caused a significant (P DME (dichloromethane/methanol extract; 36.19%) > EF (ethylacetate fraction; 20.70%) > HF (n-hexane fraction; 10.09. The methanol fraction, which showed the highest potency in oral glucose tolerance test (OGTT), was further separated into column chromatographic sub-fractions—F1, F2, F3 and F4 fractions. These sub-fractions were evaluated for antihyperglycemic activity. Sub-fractions F1, F2 and F3 (1000 mg/kg) did produce significant (P > 0.05) reduction in blood glucose level after 24 h. Sub-fraction F4 (50, 100, 200 mg/kg), however caused a significant (P 4 (74.57%) was significantly (P Newbouldia laevis possess antihyperglycemic activities and can be the basis for the folk use N. laevis in management of diabetes mellitus.

Dysfunctional astrocytes are increasingly recognized as key players in the development and progression of mesial temporal lobe epilepsy (MTLE). One of the dramatic changes astrocytes undergo in MTLE with hippocampal sclerosis (HS) is loss of gap junction coupling. To further elucidate molecular mechanism(s) underlying this alteration, we assessed expression, cellular localization and phosphorylation status of astrocytic gap junction proteins in human and experimental MTLE-HS. In addition to conventional confocal analysis of immunohistochemical staining we employed expansion microscopy, which allowed visualization of blood-brain-barrier (BBB) associated cellular elements at a sub-µm scale. Western Blot analysis showed that plasma membrane expression of connexin43 (Cx43) and Cx30 were not significantly different in hippocampal specimens with and without sclerosis. However, we observed a pronounced subcellular redistribution of Cx43 toward perivascular endfeet in HS, an effect that was accompanied by increased plaque size. Furthermore, in HS Cx43 was characterized by enhanced C-terminal phosphorylation of sites affecting channel permeability. Prominent albumin immunoreactivity was found in the perivascular space of HS tissue, indicating that BBB damage and consequential albumin extravasation was involved in Cx43 dysregulation. Together, our results suggest that subcellular reorganization and/or abnormal posttranslational processing rather than transcriptional downregulation of astrocytic gap junction proteins account for the loss of coupling reported in human and experimental TLE. The observations of the present study provide new insights into pathological alterations of astrocytes in HS, which may aid in the identification of novel therapeutic targets and development of alternative anti-epileptogenic strategies.

Background: Tuberculosis (TB) diagnosis by culture in most resource-limited settings is hampered by high contamination rate varying up to 31%. Reduction of oral microorganism loads by mouth rinse with antiseptic before sputum collection showed a reduction of contamination. Moreover, knowing the characteristic of residual contaminant microorganisms would be an asset to understand contamination issues. Objectives: The aim of this study was to evaluate the effects of mouth rinsing with chlorhexidine on mycobacteria culture contaminations and to characterize morphologically the residual contaminants. Methods: We consecutively included 158 patients in a TB center. Each of them supplied two sputa: The first before mouth rinse, and the second after 60sec of mouth rinsing with chlorhexidine (0.1%). Petroff method and Lowenstein-Jensen media were used for sputum decontamination and inoculation respectively. The contamination rates were compared, and the type of residual contaminants were characterized and compared. Results: The contamination rate did not differ before and after the mouth rinse (respectively 58/150 (39 %) vs 61/150 (41 %), p=0.7). The major residual contaminants were Gram positive spore forming bacteria (94%). Conclusion: Chlorhexidine mouth rinsing before sputum collection did not reduce mycobacterial culture contamination rate. This is probably due to spore forming bacteria, highlighted as major residual contaminants. Keywords: Oral rinse, sputum, Mycobacteria culture, contamination rate, residual contaminants.

The course of desmin-related restrictive cardiomyopathy (DRCM) during pregnancy has not been described previously because of the rarity of the condition. Following an episode of heart failure antecedent to conception, a 28-year-old primigravida with DRCM presented to establish prenatal care during the first trimester. Prenatal management consisted of β-blocker and diuretic therapy, with serial echocardiography to monitor cardiac function. Spontaneous labor ensued at 39 weeks' gestation, and vacuum-assisted delivery was performed for fetal indication. Postpartum blood transfusion was required for symptomatic anemia because of uterine atony, and subsequent maternal and neonatal courses were uncomplicated. Cardiac evaluation postpartum demonstrated stable maternal status. Pregnancy in women with controlled DRCM is not contraindicated, however, it requires careful planning and monitoring during the antenatal, intrapartum, and postpartum periods. On the basis of this report, pregnancy does not appear to exert a permanent deleterious effect on cardiac function in women with DRCM.

International audience; BackgroundThere is little data on the metabolic effects of adipokines in sub-Saharan African populations. This study aimed to explore the potential relationship of leptin and adiponectin, with obesity, plasma lipids and insulin resistance in a Cameroonian population.MethodsWe enrolled 167 men and 309 women aged ≥18 years from the general population in Cameroon. Data were collected on waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), body fat (BF%), fasting blood glucose, plasma lipids, adiponectin, leptin, insulin and homeostasis model for assessment of insulin resistance (HOMA-IR). Pearson’s correlation and multiple stepwise linear regression analyses were used to determine correlates of leptin and adiponectin serum levels.ResultsThe prevalence of obesity was higher in women compared to men (p

Purpose of review The presence of multiple diseases, polypharmacy, malnutrition, and impaired metabolism in elderly individuals increases the risks of adverse events related to drug–food interactions. Some considerations for elderly people influenced by drug–food interactions are reviewed. Recent findings When investigating pharmacokinetic and pharmacodynamic modifications in the elderly, other factors have to be considered, such as anorexia, dementia, depression, intolerance, gastrointestinal-tract disorders, social and economic factors, reduced abilities (visual and manual) and difficulties in chewing or swallowing. Specific reference is made herein to the health status of the elderly Brazilian population based on the observations of our research group. In addition, the most common diseases (such as cancer, coronary heart disease, dementia, diabetes mellitus, hypertension and osteoporosis), the drugs usually prescribed to treat them, and the adverse nutritional reactions that occur in older patients are summarized. Summary In order to develop a correct drug prescription plan and nutritional intervention to avoid any kind of undesirable drug–food interaction effect, it is necessary to adequately diagnose the disease and often re-evaluate the chosen treatment, identify disease stages and the necessary therapies to minimize the number of drugs administered, and select a reasonable nutritional assessment.

Background We aimed to investigate the molecular epidemiology of Mycobacterium tuberculosis complex (MTBC) isolates in the province of Palermo, Sicily, Italy, by characterizing 183 isolates identified in the years 2004-2012. A comparison with 104 MTBC strains identified in the same geographic area in the years 1994-2000 was also carried out. Methods One hundred eighty-three MTBC isolates identified in Palermo, Italy, in the years 2004-2012 were analyzed by spoligotyping and the 24 mycobacterial interspersed repetitive unit (MIRU)-variable-number tandem-repeat (VNTR) method typing. Susceptibility testing to streptomycin, isoniazid, rifampin and ethambutol was also performed. Furthermore, the spoligotyping dataset obtained from 104 MTBC isolates identified from 1994 to 2000 was reanalyzed. Distribution into lineages and clustering of isolates in the two periods was compared. Results One hundred seventy-seven out of the 183 isolates of MTBC submitted to molecular typing were fully characterized. Of these, 108 were from Italian-born and 69 from foreign-born individuals. Eleven different lineages and 35 families-subfamilies were identified with the most represented lineages being Haarlem (26.5%), T (19.2%), LAM (13.6%) and S (8.5%). Except for the Haarlem lineage, where isolates from foreign-born patients were overrepresented, the distribution of isolates in the families belonging to the Euro-American clone reflected the proportions of the two subpopulations. A total of 27 (15.2%) strains were clustered and three clusters were mixed. Approximately 25% of the 183 MTBC isolates under study proved to be resistant to at least one antiTB drug, with only three isolates categorized as multidrug resistant (MDR). When MTBC isolates identified in the years 1994-2000 were reanalyzed, lineages T (30.8%), LAM (29.8%), Haarlem (16.3%) and S (13.5%) proved to be predominant. No MTBC isolates belonging to CAM, U, CAS, Turkish and Ural lineages were identified. Conclusions A wide heterogeneity was detected among the MTBC strains isolated in the years 2004-2012. Six lineages were not present among the isolates of the period 1994-2000. Comparison between distribution of lineages in the two consecutive periods depicts rapid and deep changes in the TB epidemiology in Palermo, Italy. An universal and continued laboratory-based surveillance of TB in Sicily is required. Electronic supplementary material The online version of this article (doi:10.1186/s12879-014-0602-4) contains supplementary material, which is available to authorized users.

Glial cells are now recognized as active communication partners in the central nervous system, and this new perspective has rekindled the question of their role in pathology. In the present study we analysed functional properties of astrocytes in hippocampal specimens from patients with mesial temporal lobe epilepsy without (n = 44) and with sclerosis (n = 75) combining patch clamp recording, K(+) concentration analysis, electroencephalography/video-monitoring, and fate mapping analysis. We found that the hippocampus of patients with mesial temporal lobe epilepsy with sclerosis is completely devoid of bona fide astrocytes and gap junction coupling, whereas coupled astrocytes were abundantly present in non-sclerotic specimens. To decide whether these glial changes represent cause or effect of mesial temporal lobe epilepsy with sclerosis, we developed a mouse model that reproduced key features of human mesial temporal lobe epilepsy with sclerosis. In this model, uncoupling impaired K(+) buffering and temporally preceded apoptotic neuronal death and the generation of spontaneous seizures. Uncoupling was induced through intraperitoneal injection of lipopolysaccharide, prevented in Toll-like receptor4 knockout mice and reproduced in situ through acute cytokine or lipopolysaccharide incubation. Fate mapping confirmed that in the course of mesial temporal lobe epilepsy with sclerosis, astrocytes acquire an atypical functional phenotype and lose coupling. These data suggest that astrocyte dysfunction might be a prime cause of mesial temporal lobe epilepsy with sclerosis and identify novel targets for anti-epileptogenic therapeutic intervention.

Introduction:for a high quality level diagnosis, mycobacterium culture must comply with the pre-analytical and analytical conditions recommended by the WHO and the country National Tuberculosis Program (NTP). In this study, we determined whether temperature and duration of sputum storage were associated with culture contamination in Burkina Faso. Methods:sputa were collected in 5 districts labs in Burkina Faso. Temperature and duration of sputum storage were recorded. After the collection, sputa were decontaminated using Petroff modified method, and the pellet was inoculated on LJ media and LJ media supply with 2% sodium pyruvate. Risk of culture contamination associated with temperature and duration of sputum storage was measured by Chi2 test and logistic regression. Results:out of 404 specimens, 61% (246/404) were stored between 2 and 8°C, and 15% (61/404) were processed within three days. The global contamination rate was 24%, with only 8% for samples respecting WHO recommendations, up to 35% for others. Storage at room temperature was associated with a significantly higher risk of contamination compared to storage at 2-8°C (OR 2.24, p=0.001, IC 95%). Conclusion:the recommendations about the temperature and the duration of sputum storage before cultures are not completely respected. This leads to high contamination rate of mycobacterium culture. It will be necessary to take logistics measures in peripherals health services or to develop more selective medium for mycobacterium culture in low income countries.

Fluoroquinolones are the core drugs for the management of multidrug-resistant tuberculosis (MDR-TB). Molecular drug susceptibility testing methods provide considerable advantages for scaling up programmatic management and surveillance of drug-resistant TB. We describe here the misidentification of fluoroquinolone resistance by the GenoType MTBDR sl (MTBDR sl ) (Hain Lifescience GmbH, Nehren, Germany) line probe assay (LPA) encountered during a feasibility and validation study for the introduction of this rapid drug susceptibility test in Kinshasa, Democratic Republic of Congo. The double gyrA mutation 80Ala and 90Gly represented 57% of all fluoroquinolone mutations identified from MDR-TB patient sputum samples, as confirmed by DNA sequencing. This double mutation was previously found to be associated with susceptibility to fluoroquinolones, yet it leads to absent hybridization of a wild-type band in the MTBDR sl and is thus falsely scored as resistance. Our findings suggest that MTBDR sl results must be interpreted with caution when the interpretation is based solely on the absence of a wild-type band without confirmation by visualization of a mutant band. Performance of the MTBDR sl LPA might be improved by replacing the gyrA wild-type probes by additional probes specific for well-documented gyrA mutations that confer clinically relevant resistance.

Tuberculosis (TB) is still a serious public health problem, continuing to be an important threat for confined populations. We used spoligotyping to estimate the genotypic clades of Mycobacterium tuberculosis isolates from inmates in two blocks in a southeastern Brazilian prison unit, with TB incidence rate of 8185/100.000. The Latin American Mediterranean (LAM) clade is well represented in the country, and the LAM specific molecular markers, RD Rio large sequence polymorphism and the SNP on the Rv3062 [ligB 1212 ], were used to characterize spoligotype signatures from prison isolates. Typing of RD Rio and ligB increase LAM clade from 66.7% ( n = 72/108) to 69.4% ( n = 75). The LAM2 SIT17 ( n = 23) and SIT179 ( n = 12) signatures comprised one third of all isolates, followed by Haarlem (11.5%, n = 12), T (8.7%, n = 9) and X (5.7%, n = 6) clades. Strains with unknown signatures represented 5.5% ( n = 6), and four (3.7%) did not match any lineage. We observed RD Rio among 64 (59.2%) isolates, and 54 (50%) were of the LAM clade. In particular, the LAM2/RD Rio sub-lineage was significantly associated with clustering ( p = 0.02) and its frequency was higher (32%) when compared to that of the previous general TB cases in RJ (4.29%). Overall cluster frequency defined by spoligotyping/IS6110-RFLP was 62%. The two evolutionary markers helped to evaluate some LAM signature misconceptions and demonstrate that LAM2/RD Rio was found with high frequency, hitherto being unnoticed. All these data, allied to high clustering, imply that public health measures to minimize the escalation of TB in prison is essential, and both spoligotyping as well as RD Rio would be useful tools to monitor the effects of the measures with respect to M. tuberculosis lineage variation.

International audience; Rio de Janeiro is endemic for tuberculosis (TB) and presents the second largest prevalence of the disease in Brazil. Here, we present the bacterial population structure of 218 isolates of Mycobacterium tuberculosis, derived from 186 patients that were diagnosed between January 2008 and December 2009. Genotypes were generated by means of spoligotyping, 24 MIRU-VNTR typing and presence of fbpC103, RDRio and RD174. The results confirmed earlier data that predominant genotypes in Rio de Janeiro are those of the Euro American Lineages (99%). However, we observed differences between the classification by spoligotyping when comparing to that of 24 MIRU-VNTR typing, being respectively 43.6% vs. 62.4% of LAM, 34.9% vs. 9.6% of T and 18.3% vs. 21.5% of Haarlem. Among isolates classified as LAM by MIRU typing, 28.0% did not present the characteristic spoligotype profile with absence of spacers 21 to 24 and 32 to 36 and we designated these conveniently as "LAM-like", 79.3% of these presenting the LAM-specific SNP fbpC103. The frequency of RDRio and RD174 in the LAM strains, as defined both by spoligotyping and 24 MIRU-VNTR loci, were respectively 11% and 15.4%, demonstrating that RD174 is not always a marker for LAM/RDRio strains. We conclude that, although spoligotyping alone is a tool for classification of strains of the Euro-American lineage, when combined with MIRU-VNTRs, SNPs and RD typing, it leads to a much better understanding of the bacterial population structure and phylogenetic relationships among strains of M. tuberculosis in regions with high incidence of TB.

As a follow-up of the “spoligoriftyping” development, we present here an extension of this technique which includes the detection of isoniazid resistance-associated mutations in a new 59-plex assay, i.e., tuberculosis-spoligo-rifampin-isoniazid typing (TB-SPRINT), running on microbead-based multiplexed systems. This assay improves the synergy between clinical microbiology and epidemiology by providing (i) mutation-based prediction of drug resistance profiles for patient treatment and (ii) genotyping data for tuberculosis (TB) surveillance. This third-generation microbead-based high-throughput assay for TB runs on the Luminex 200 system and on the recently launched MagPix system (Luminex, Austin, TX). Spoligotyping patterns obtained by the TB-SPRINT method were 100% ( n = 85 isolates; 3,655/3,655 spoligotype data points) concordant with those obtained by microbead-based and membrane-based spoligotyping. Genetic drug susceptibility typing provided by the TB-SPRINT method was 100% concordant with resistance locus sequencing ( n = 162 for rpoB gene sequencing and n = 76 for katG and inhA sequencing). Considering phenotypic drug susceptibility testing (DST) as the reference method, the sensitivity and specificity of TB-SPRINT regarding Mycobacterium tuberculosis complex ( n = 162 isolates) rifampin resistance were both 100%, and those for isoniazid resistance were 90.4% (95% confidence interval, 85 to 95%) and 100%, respectively. Used routinely in national TB reference and specialized laboratories, the TB-SPRINT assay should simultaneously improve personalized medicine and epidemiological surveillance of multidrug-resistant (MDR) TB. This assay is expected to play an emerging role in public health in countries with heavy burdens of MDR TB and/or HIV/TB coinfection. Application of this assay directly to biological samples, as well as development for extensively drug-resistant (XDR) TB detection by inclusion of second-line antituberculosis drug-associated mutations, is under development. With bioinformatical methods and data mining to reduce the number of targets to the most informative ones, locally adapted formats of this technique can easily be developed everywhere.

In the actual context of increasing tuberculosis and anti-tuberculosis drug resistance, the laboratory diagnosis of Mycobacterial infections remain the primordial objective of control and surveillance of human tuberculosis. The diagnosis and following of tuberculosis in resource limited settings are done by microscopy Ziehl-Neelsen method which is poor sensitive (20-53%) and have poor specificity because it's can't distinguish tuberculosis mycobacterium and atypical tuberculoid mycobacterium. Mycobacterium culture on solid media is the gold standard method for tuberculosis and anti-tuberculosis drug resistance diagnosis. Here, the challenge is that expectorations using for culture contain mycobacterium and others contaminating bacteria responsible of culture contamination. Many different methods of homogenization and decontamination of sputum specimens for culturing exist and each laboratory had to do a choice of the better method to optimize isolating of mycobacterium. This review is a summary of homogenization and decontamination methods described in literature and used by certain laboratories for diagnosis of TB by culture. However, it's essential for each laboratory to conduct evaluation of the different methods and do the choice of the appropriate one by taking into account factors such as the feasibility and cost effectively. Nine methods of decontaminations are described in this review taking account of their advantages, drawbacks and their feasibility in resource limited settings.

Objective The hypertension epidemic in Africa collectively with very low rates of blood pressure control may predict an incremented prevalence of resistant hypertension (RH) across the continent. The aim of this study was to determine the prevalence of RH and associated risk factors in Africa. Data sources We conducted a comprehensive search of electronic databases (PubMed, EMBASE, Africa Wide Information and Africa Index Medicus) completed by manual search of articles, regardless of language or publication date. Methods We included studies which have reported the prevalence and/or risk factors for RH in Africa from inception to 19 May 2016. Forest plots were drawn to visualise the combined prevalence of RH and extent of statistical heterogeneity between studies. Results Out of 259 retrieved studies, only 5 from Cameroon, Nigeria, Burkina Faso, Lesotho and Algeria with a total population of 4 068 patients were finally included in this review. There was no study from the Eastern part of Africa. Though the definition of RH was not similar across studies, its prevalence was respectively 11.7%, 4.9%, 14.6%, 14.3% and 19.0%, with an overall pooled prevalence of 12.1% (95% CI 8.0% to 17.7%). Potential risk factors were: non-compliance to treatment, ageing, male sex, dyslipidaemia, metabolic syndrome, previous cardiovascular events, physical inactivity and stress, but not excessive salt intake, alcohol and coffee ingestions. Moreover, diabetes, smoking, obesity and renal insufficiency yielded discrepant results. Conclusions There is a huge dearth of research on the epidemiology of RH in Africa. Thereby, an extensive study of RH prevalence and risk factors is still largely warranted to curtail the high and continuously increasing burden of hypertension across Africa.

International audience; BACKGROUND: Nigeria has the tenth highest burden of tuberculosis (TB) among the 22 TB high-burden countries in the world. This study describes the biodiversity and epidemiology of drug-susceptible and drug-resistant TB in Ibadan, Nnewi and Abuja, using 409 DNAs extracted from culture positive TB isolates. METHODOLOGY/PRINCIPAL FINDINGS: DNAs extracted from clinical isolates of Mycobacterium tuberculosis complex were studied by spoligotyping and 24 VNTR typing. The Cameroon clade (CAM) was predominant followed by the M. africanum (West African 1) and T (mainly T2) clades. By using a smooth definition of clusters, 32 likely epi-linked clusters related to the Cameroon genotype family and 15 likely epi-linked clusters related to other "modern" genotypes were detected. Eight clusters concerned M. africanum West African 1. The recent transmission rate of TB was 38%. This large study shows that the recent transmission of TB in Nigeria is high, without major regional differences, with MDR-TB clusters. Improvement in the TB control programme is imperative to address the TB control problem in Nigeria.

International audience; Using Ziehl-Neelsen-positive slides collected from tuberculosis diagnostic centers in Burkina Faso, we showed that 20% of 80 spoligotyping-positive DNA samples had a characteristic Mycobacterium africanum-specific genomic signature. This result suggests that M. africanum is still present in Burkina Faso at almost the same prevalence as 15-20 years ago.

Because the risk of venous thromboembolism (VTE) associated with progestin is uncertain, we tested oral contraceptives, estrogen and progestin as independent VTE risk factors.Using longitudinal, population-based Rochester Epidemiology Project resources, we identified all Olmsted County, MN women with objectively-diagnosed incident VTE over the 13-year period, 1988-2000 (n=726) and one to two Olmsted County women per case matched on age, event year and duration of prior medical history (n=830), and reviewed their complete medical history in the community for previously-identified VTE risk factors (i.e., hospitalization with or without surgery, nursing home confinement, trauma/fracture, leg paresis, active cancer, varicose veins and pregnancy/postpartum), and oral contraceptive, oral estrogen, and oral or injectable progestin exposure. Using conditional logistic regression we tested these hormone exposures as VTE risk factors, both unadjusted and after adjusting for previously-identified VTE risk factors.In unadjusted models, oral contraceptives, progestin alone, and estrogen plus progestin were significantly associated with VTE. Individually adjusting for body mass index (BMI) and previously-identified VTE risk factors, these effects remained essentially unchanged except that progestin alone was not associated with VTE after adjusting for active cancer. Considering only case-control pairs without active cancer, progestin alone was positively but non-significantly associated with VTE (OR=2.49; p=0.16). Adjusting for BMI and previously-identified VTE risk factors including active cancer, oral contraceptives, estrogen alone, and progestin with or without estrogen were significantly associated with VTE.Oral contraceptives, estrogen alone, estrogen plus progestin, and progestin with or without estrogen are independent VTE risk factors.

Summary Between October 2004 and January 2005, 144 patients with peritonitis were admitted to the surgical wards of Kinshasa General Hospital and a few private city clinics. 63 patients (44%) underwent surgical intervention because of intestinal perforation consistent with typhoid fever; the case fatality rate was 53%. The majority of patients had received a course of first-line antibiotics such as chloramphenicol, ampicillin or co-trimoxazole before admission. On bacteriological investigation, Salmonella Typhi was isolated from the blood of 11 patients with peritonitis. The isolates were all resistant to ampicillin, chloramphenicol, tetracycline and co-trimoxazole, but sensitive to third-generation cephalosporins, quinolone (nalidixic acid, ciprofloxacine) and amoxicillin-clavulanic acid. Several factors contributed to the poor outcome of this disease including a) the use of inappropriate antibiotics, b) long delay in diagnosis, c) difficult access to health facilities. This is the first documented outbreak of typhoid fever caused by a multidrug-resistant S. Typhi in Kinshasa.

Abstract Wilkie syndrome or superior mesenteric artery syndrome is a rare cause of duodenal obstruction in pediatric and adult age groups. Its manifestations are due to compression of the third portion of the duodenum between the aorta and the superior mesenteric artery. We present one case of a 29-year-old female with a recent history of epigastric pain and severe weight loss due to duodenal obstruction from superior mesenteric syndrome. She was treated conservatively with jejunostomy tube feeding to regain loss of weight. Our case is unique in that the patient has also nutcracker syndrome.

BACKGROUND Cognitive dysfunction is a well known problem in the postoperative period in cardiac surgery. We hypothesised that the incidence of postoperative cognitive dysfunction in patients with diabetes mellitus is higher than in the nondiabetic patient. METHODS Thirty-four patients (11 females, 23 males) with a mean age of 62.44 +/- 7.52 undergoing on-pump CABG surgery were studied in a prospective manner. Fourteen patients had treated diabetes mellitus (Group I) and 20 were nondiabetic (Group II). All patients were operated upon by the same surgeon under standardised intra- and perioperative conditions. Patients with preoperative dementia (MMSE < 24) or advanced cerebrovascular disease were excluded. An extensive set of tests examining emotional and cognitive state, stress-coping and quality of life were performed preoperatively. Emotional and cognitive variables were assessed daily from day two to five postoperatively. RESULTS All tests showed comparable results between the groups preoperatively. The perfusion lasted considerably longer in Group I (102.5 +/- 16.61 vs. 83.9 +/- 14.1 min) as did the cross clamping (64.21 +/- 18.31 vs. 51.75 +/- 10.88 min). Postoperative cognitive outcome was significantly worse in Group I with regard to the Stroop Test (29.46 +/- 8.6 vs. 24.01 +/- 6.23, P = 0.02), the Abbreviated Mental Test (8.04 +/- 0.71 vs. 8.68 +/- 0.78, P = 0.02) and the Trial Making Test (35.72 +/- 11.38 vs. 29.3 +/- 7.77 P = 0.04). These differences persisted even after adjustment for perfusion- and cross-clamping time. CONCLUSION The cognitive outcome in the early postoperative period is worse in diabetic patients compared to nondiabetics. Speed-related cognitive functions are mainly affected. Probably, this reflects a different physiology of cerebral perfusion during extracorporeal circulation. Optimising perfusion strategies to improve the outcome of diabetic patients should be the next topic of study.

Background: Multidrug resistance is a critical factor in tuberculosis control. To gain better understanding of multidrug resistant tuberculosis in Brazil, a retrospective study was performed to compare genotypic diversity and drug resistance associated mutations in Mycobacterium tuberculosis isolates from a national reference center. Methods and Findings: Ninety-nine multidrug resistant isolates from 12 Brazilian states were studied. Drug-resistance patterns were determined and the rpoB and katG genes were screened for mutations. Genotypic diversity was investigated by IS6110-RFLP and Luminex 47 spoligotyping. Mutations in rpoB and katG were seen in 91% and 93% of the isolates, respectively. Codon 315 katG mutations occurred in 82.8% of the isolates with a predominance of the Ser315Thr substitution. Twenty-five isolates were clustered in 11 groups with identical IS6110-RFLP patterns while 74 showed unique patterns with no association between mutation frequencies or susceptibility profiles. The most prevalent spoligotyping lineages were LAM (47%), T (17%) and Haarlen (12%). The Haarlen lineage showed a higher frequency of codon 516 rpoB mutations while codon 531 mutations prevailed in the other isolates. Conclusions: Our data suggest that there were no major multidrug resistant M. tuberculosis strains transmitted among patients referred to the reference center, indicating an independent acquisition of resistance. In addition, drug resistance associated mutation profiles were well established among the main spoligotyping lineages found in these Brazilian multidrug resistant isolates, providing useful data for patient management and treatment.

Multidrug Resistant Tuberculosis (MDR-TB) is a serious threat which jeopardizes the worldwide efforts to control TB. The Democratic Republic of Congo (DRC) is one of 27 countries with a high burden of MDR-TB. Data on the magnitude, trends, and the distribution of MDR-TB in DRC are scanty. Kinshasa, the capital city of DRC which accounts for 20% of all TB cases nationwide, is notifying more than 80% of all MDR suspects. We report here a cluster of MDR-TB cases that was investigated in the Mosango health district, in the Bandundu south Province, DRC in 2008. Phenotypic Drug Sensitivity Testing and DNA sequencing were performed on 18 sputum specimens collected from 4 MDR-TB suspects and 5 household contacts. Sequencing data confirmed that the 4 suspects were indeed Rifampicin resistant cases. Sequencing of the rpoB gene showed that 3 cases (patients A, B and D) had a single mutation encoding a substitution to 526Tyr, 531Trp and 526Leu respectively. Patient C had a double mutation encoding a change to 531Leu and 633Leu. Two of the investigated cases died within 4 months of a second-line treatment course. Results highlight the need to enhance adequate laboratory services within the country for both clinical as well as surveillance purposes.

[Figure][1] A 75-year-old woman with a history of a large infrascapular congenital arteriovenous malformation (AVM) presented with progressive fatigue and weakness. Treadmill stress echocardiography and right and left heart catheterization were unremarkable. Cardiovascular examination