A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms.

BACKGROUND: Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale. METHODS: We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci. RESULTS: We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay. CONCLUSIONS: No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).

Epidemiology of malaria in an area of seasonal transmission in Niger and implications for the design of a seasonal malaria chemoprevention strategy.

BACKGROUND: Few data are available about malaria epidemiological situation in Niger. However, implementation of new strategies such as vaccination or seasonal treatment of a target population requires the knowledge of baseline epidemiological features of malaria. A population-based study was conducted to provide better characterization of malaria seasonal variations and population groups the most at risk in this particular area. METHODS: From July 2007 to December 2009, presumptive cases of malaria among a study population living in a typical Sahelian village of Niger were recorded, and confirmed by microscopic examination. In parallel, asymptomatic carriers were actively detected at the end of each dry season in 2007, 2008 and 2009. RESULTS: Among the 965 presumptive malaria cases recorded, 29% were confirmed by microscopic examination. The incidence of malaria was found to decrease significantly with age (p < 0.01). The mean annual incidence was 0.254. The results show that the risk of malaria was higher in children under ten years (p < 0.0001). The number of malaria episodes generally followed the temporal pattern of changes in precipitation levels, with a peak of transmission in August and September. One-thousand and ninety subjects were submitted to an active detection of asymptomatic carriage of whom 16% tested positive; asymptomatic carriage decreased with increasing age. A higher prevalence of gametocyte carriage among asymptomatic population was recorded in children aged two to ten years, though it did not reach significance. CONCLUSIONS: In Southern Niger, malaria transmission mostly occurs from July to October. Children aged two to ten years are the most at risk of malaria, and may also represent the main reservoir for gametocytes. Strategies such as intermittent preventive treatment in children (IPTc) could be of interest in this area, where malaria transmission is highly seasonal. Based on these preliminary data, a pilot study could be implemented in Zindarou using IPTc targeting children aged two to ten years, during the three months of malaria transmission, together with an accurate monitoring of drug resistance.

A refined estimate of the malaria burden in Niger.

BACKGROUND: The health authorities of Niger have implemented several malaria prevention and control programmes in recent years. These interventions broadly follow WHO guidelines and international recommendations and are based on interventions that have proved successful in other parts of Africa. Most performance indicators are satisfactory but, paradoxically, despite the mobilization of considerable human and financial resources, the malaria-fighting programme in Niger seems to have stalled, as it has not yet yielded the expected significant decrease in malaria burden. Indeed, the number of malaria cases reported by the National Health Information System has actually increased by a factor of five over the last decade, from about 600,000 in 2000 to about 3,000,000 in 2010. One of the weaknesses of the national reporting system is that the recording of malaria cases is still based on a presumptive diagnosis approach, which overestimates malaria incidence. METHODS: An extensive nationwide survey was carried out to determine by microscopy and RDT testing, the proportion of febrile patients consulting at health facilities for suspected malaria actually suffering from the disease, as a means of assessing the magnitude of this problem and obtaining a better estimate of malaria morbidity in Niger. RESULTS: In total, 12,576 febrile patients were included in this study; 57% of the slides analysed were positive for the malaria parasite during the rainy season, when transmission rates are high, and 9% of the slides analysed were positive during the dry season, when transmission rates are lower. The replacement of microscopy methods by rapid diagnostic tests resulted in an even lower rate of confirmation, with only 42% of cases testing positive during the rainy season, and 4% during the dry season. Fever alone has a low predictive value, with a low specificity and sensitivity. These data highlight the absolute necessity of confirming all reported malaria cases by biological diagnosis methods, to increase the accuracy of the malaria indicators used in monitoring and evaluation processes and to improve patient care in the more remote areas of Niger. This country extends over a large range of latitudes, resulting in the existence of three major bioclimatic zones determining vector distribution and endemicity. CONCLUSION: This survey showed that the number of cases of presumed malaria reported in health centres in Niger is largely overestimated. The results highlight inadequacies in the description of the malaria situation and disease risk in Niger, due to the over-diagnosis of malaria in patients with simple febrile illness. They point out the necessity of confirming all cases of suspected malaria by biological diagnosis methods and the need to take geographic constraints into account more effectively, to improve malaria control and to adapt the choice of diagnostic method to the epidemiological situation in the area concerned. Case confirmation will thus also require a change in behaviour, through the training of healthcare staff, the introduction of quality control, greater supervision of the integrated health centres, the implementation of good clinical practice and a general optimization of the use of available diagnostic methods.

[Dental care and joint prostheses]. / Soins bucco-dentaires et prothèses articulaires.

PURPOSE OF THE STUDY: Infectious dental foci and oral dental care constitute one of the leading causes of arthroplasty infection after infections involving the skin and the urinary tract. There is however no formal evidence confirming the relationship between oral or dental care and arthroplasty infection. MATERIAL AND METHODS: We reviewed 44 cases of arthroplasty infection secondary to dental infections and searched for data in the literature. In our series, no risk factor could be identified for 24 cases. The median disease-free interval was five years and mean time from the oral-dental procedure to the first signs of prosthesis infection was one month. Tooth extraction was the most common oral-dental procedure involved (n=19). Most of the infections were caused by a single agent, predominantly Streptococci sp. (n=24) and Staphylococci sp. (n=12). DISCUSSION: It is well known that dental-related bacteriemia is a spontaneous daily event even without dental procedures. It is also probable that spontaneous bacteriemia induced by daily activities is much more frequent than dental-care induced bacteriemia. The presence of foreign material diminishes local antibacterial defense systems increasing the risk of hematogeneous contamination of the joint prosthesis after dental care. The oral flora is also modified in immunodepressed subjects, particularly carriage of Staphylococcus aureus in the oral cavity which is significantly more frequent in patients with rheumatoid arthritis. These changes increase the risk of contamination after dental care. For arthroplasty infection, the pathogenic power of Staphylococci sp. is certainly greater than that of Streptococci sp. even if the inoculum is less abundant. Antibiotic prophylaxis during dental care in patients with an arthroplasty remains a controversial subject and the most appropriate antibiotic remains to be defined. Successive episodes of spontaneous bacteriemia arising from an oral-dental foci are probably the main cause of arthroplasty infections, more so than bacteriemia triggered by dental care. CONCLUSION: Antibiotic therapy is not indicated for routine dental care in the majority of patients but is recommended whenever there is a high risk of arthroplasty contamination. In the event of oral-dental infection, antibiotic therapy is necessary. The recommendations proposed by the ADA and the AAOS were revised in 2003. The most important point is to obtain and maintain a good state of oral hygiene. For prevention, awareness of the risk is essential, for the patient, the orthopedic surgeon and the primary care physician alike. Regular dental visits are necessary.

[Impact of CRP rapid test in management of febrile children in paediatric emergency units of Ile-de-France]. / Impact de la protéine C-réactive (CRP) en microméthode sur la prise en charge des enfants fébriles aux urgences pédiatriques en Ile-de-France.

OBJECTIVE: Fever is a common cause of children visits to emergency units. Clinical evaluation does not always eliminate a bacterial infection. Among blood markers, several publications showed the interest of CRP. This study was undertaken to evaluate correlation between two techniques of CRP, one by usual technique at the laboratory and the other by a rapid test, and to evaluate the impact of this rapid test for febrile children at the emergency room, when a hospitalization was not immediately decided. MATERIAL AND METHODS: The study was undertaken in 2004-2005 in eight emergency paediatric units in Ile-de-France concerning febrile children during two periods. In period A, children had at the same time a CRP dosage through two methods, whereas in period B, only a rapid CRP test was first managed. The test used was NycoCard CRP Single test (Progen Biotechnique). RESULTS: Between September 2004 and June 2005, 572 children were included, 268 in period A and 304 in period B. Comparison of CRP results by the two methods showed for 247 children (93%) a fairly good linear correlation (r: 0.929). Blood cell count was the most often prescribed test (99.4 vs 10.5%). Conversely to chest radiography, blood culture, fibrinogen and urinary test were significantly most frequent in period A. The average cost of the additional examinations was 2.6 times more important during the first period. Duration of children management in the units was approximately two times shorter when rapid CRP test was used (199.7+/-92.8 vs 103.5+/-98.6 min). CONCLUSION: This study shows the interest of rapid CRP test for febrile children in the emergency units, and has to be confirmed in ambulatory paediatric practice.

Possible involvement of gelatinase A (MMP2) and gelatinase B (MMP9) in toxic epidermal necrolysis or Stevens-Johnson syndrome.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are considered to be drug-induced diseases, and are characterized by extensive mucocutaneous disorder and epidermal necrosis which result in the detachment of the epidermis. Inactive and active forms of metalloproteinases (MMP2 and MMP9) secreted by skin explants maintained in organ culture for 72 h and in blister fluid from two TEN and three SJS patients were investigated. Interestingly, lesional skin from both the TEN and the SJS patients cultured for 3 days in conditioned medium showed high levels of both 72 kDa progelatinase A and 66 kDa activated gelatinase A, and the 66 kDa activated form was not observed in cultures of skin from control individuals. Furthermore, indirect immunodetection showed the presence of MMP2 and MMP9 in TEN and SJS patients' skin. Increased gelatinase activity in the culture medium of TEN and SJS skin maintained in organ culture and in blister fluid indicates that these gelatinases may be responsible for the detachment of the epidermis in these drug-induced necrolyses.

The lower labial branches of the mental nerve: anatomic variations and surgical relevance.

PURPOSE: The purpose of this study was to determine the cause of injuries of the lower labial branches (LLB) of the mental nerve (MN) after biopsy of minor salivary glands (BMSG), labial nodule excision, or symphyseal bone procedures using a labial approach. PATIENTS AND METHODS: Thirty-two MN were dissected in 16 cadavers to trace the labial branches. The following factors were recorded: 1) the number of LLB; 2) the angle between the medial LLB and the fibers of the orbicularis oris muscle; 3) the anastomoses between the lateral branches; and 4) the midline crossover innervation of the LLB. The number of branches on each side, as well as values of the angle between the nerves and superficial fibers of the orbicularis oris muscle, were compared using the Wilcoxon test. RESULTS: The mean number of LLB was 2 (SEM, 1; range, 1 to 4); the average angle between the medial LLB and the fibers of the orbicularis oris muscle was 36 degrees (SEM, 2 degrees ), without any statistical difference between the two sides (P = .78); an anastomosis between the 2 lateral branches of the LLB was observed in only 1 case; and the mean midline crossover innervation of the LLB was 25% (SEM, 14%) of the intercommisural distance. This crossover innervation was present only on the ventral surface of the lip. CONCLUSIONS: These data suggest that injuries to the LLB could be prevented if the incision(s) are made horizontally on the dorsal aspect of the lower lip, and the angle between the incision and the long axis of the lip is approximately 36 degrees . In the case of symphyseal bone procedures using a labial route, a "U"-shaped incision parallel to the LLB is suggested.

An unusual case of a relationship between rosacea and dental foci.

Rosacea is a chronic disorder affecting the facial convexities, characterized by frequent flushing, persistent erythema, and telangiectases. During episodes of inflammation, additional features are swelling, papules, and pustules. The exact etiology of this dermatitis is unknown, and theories abound. Infectious foci, especially dental foci, seem to be rarely associated with the onset and progression of this disease. Dermatologic treatments are determined by the severity of the disease. But eradication of infectious foci, and in this case eradication of dental foci, may generate a significant improvement and may lead to a recovery.

An unusual case of alopecia areata of dental origin.

The relationship between dental foci of infectious or mechanical nature and alopecia areata is analyzed through this case. There are many different causes for this dermatologic disease, and a dental origin seems to be very uncommon. Such a cause can only be confirmed a posteriori by a complete recovery of the patient after the dental cause is removed.

Modulation of polymorphonuclear leukocyte responsiveness by copper (II)2 (niflumate)4.

Antiinflammatory activities and modulations of PMNL responses produced by treatment with tetrakis-mu-2-[3-(trifluoromethyl)-phenyl]aminonicotinatodicopper (II) [Cu(II)2(niflumate)4] and niflumic acid were studied in isologous serum-induced rat pleurisy. Doses of 10 or 30 mg/kg (35 or 106 mumol/kg) of niflumic acid or Cu(II)2(niflumate)4 (8 or 23 mumol/kg) caused significant (p < 0.01) reductions in pleural exudate and number of polymorphonuclear leukocytes (PMNLs) in the exudate. While both doses of Cu(II)2(niflumate)4 produced significant dose-related reductions in both parameters, only the higher dose of niflumic acid produced a significant dose-related reduction in both parameters. Boyden chamber measurements of N-formyl-methionyl-leucyl-phenylalanine (f-MLP) chemotaxis by PMNLs incubated with 10 or 30 micrograms/ml niflumic acid (35 or 106 nmol/ml) or Cu(II)2(niflumate)4 (8 or 23 nmol/ml) were significantly (p < 0.01 to p < 0.001) decreased in dose-related fashions. Chemotaxis of PMNLs from pleuritic rats treated orally with 10 or 30 mg/kg niflumic acid or Cu(II)2(niflumate)4 was significantly (p < 0.001) inhibited by the larger dose of niflumic acid and both doses of Cu(II)2(niflumate)4. Opsonized zymosan (OZ)-stimulated chemiluminescence (CL) of PMNLs from pleuritic rats treated orally with these same doses of niflumic acid or Cu(II)2(niflumate)4 was only significantly (p < 0.05 or p < 0.01 respectively) decreased by the larger doses. Superoxide (O2-) production by these cells was significantly decreased by the larger dose of niflumic acid (p < 0.05) while both doses of Cu(II)2(niflumate)4 produced significant (p < 0.05 to p < 0.01) decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of some non-steroidal anti-inflammatory drug copper complexes on polymorphonuclear leukocyte oxidative metabolism.

Interaction between anti-inflammatory drugs and reactive oxygen metabolites must be considered in the course of pharmacological studies intended to develop new compounds. Effects of indomethacin, aspirin, and 3,5-diisopropylsalicylic acid (3,5-DIPS) and their copper complexes on PMNL oxidative metabolism and the evolution of an acute inflammatory reaction were studied in the rat. Experiments were performed in vitro by assessment of superoxide generation and reduction of chemiluminescence by PMNLs incubated or not (control) in medium containing various concentrations of these compounds. A dose-related decrease of these parameters was observed, however, copper complexes were found to be more effective than their parent drugs or Cu gluconate. Copper complexes were also more effective anti-inflammatory agents than their parent ligands or Cu gluconate when the volume of exudate and number of exudate PMNLs were assessed after induction of pleurisy in rats by injection of isologous serum. It is concluded that modulation of the PMNL oxidative burst by copper complexes offers an accounting for the anti-inflammatory activity of these compounds.