Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria.

BACKGROUND: In erythropoietic protoporphyria (EPP), an inherited disease of porphyrin-biosynthesis, the accumulation of protoporphyrin in the skin causes severely painful phototoxic reactions. Symptom prevention was impossible until recently when afamelanotide became available. Afamelanotide-induced skin pigmentation has statistically significantly improved light-tolerance, although the clinical significance of the statistical effect was unknown. OBJECTIVES: To assess clinical effectiveness by recording compliance and safety during prolonged use. METHODS: We report longitudinal observations of 115 ambulatory patients with EPP, who were treated with a total of 1023 afamelanotide implants over a period of up to 8 years at two porphyria centres; one in Rome, Italy, and the other in Zurich, Switzerland. RESULTS: Since the treatment first became available in 2006, the number of patients treated with 16 mg afamelanotide implants rose continuously until June 2014, when 66% of all patients with EPP known to the porphyria centres were treated. Only three patients considered afamelanotide did not meet their expectations for symptom improvement; 23% discontinued the treatment for other, mostly compelling, reasons such as pregnancy or financial restrictions. The quality of life (QoL) scores, measured by an EPP-specific questionnaire, were 31 ± 24% of maximum prior to afamelanotide treatment, rose to 74% after starting afamelanotide and remained at this level during the entire observation period. Only minor adverse events attributable to afamelanotide, predominantly nausea, were recorded. CONCLUSION: Based on the improved QoL scores, high compliance and low discontinuation rates, we conclude that afamelanotide exhibits good clinical effectiveness and good safety in EPP under long-term routine conditions.

Medical check-up of newly arrived unaccompanied minors: A dedicated pediatric consultation service in a hospital.

BACKGROUND AND AIMS: Healthcare for the increasing number of migrants in Europe, and particularly of unaccompanied minors (UMs) seeking asylum, has become a major challenge. We aimed to describe the health issues of UMs managed in a dedicated pediatric consultation service in a care center in Paris. METHODS: All UMs attending a dedicated migrant medical consultation service in Robert Debré Hospital, Paris, France, were included in a single-center retrospective observational study from September 1, 2017, to September 30, 2018. RESULTS: Out of the 107 UMs who were included, 87% had a health problem (n=93) and 52% had an infectious disease (n=56). The main infectious diagnoses were schistosomiasis (22%), latent tuberculosis (22%), intestinal parasitosis (16%), and chronic hepatitis B (8%). Posttraumatic stress disorder (PTSD) and overweight were common (35% and 20%, respectively). The median age was 15 years old (IQR, 14-16), the male/female ratio was 95/12. Most of the children were from sub-Saharan Africa (n=67), 46% had crossed Libya (n=49) and, when compared to the other migration routes, faced an increasing risk of violence (69%, p=0.04), imprisonment (53%, p=0.03), and forced labor (48%, p=0.02). The median duration of the trip before reaching France was 6 months (IQR, 2-13), the median time to consultation was 2 months (0-5) and was not associated with an increased risk of health problems. A total of 43 UMs were lost to follow-up. CONCLUSION: Health problems, particularly infectious diseases and PTSD, are common among UMs and should prompt an early medical consultation with psychiatric evaluation. Follow-up is problematic and could be improved by an on-line health book.

New guidelines for the prevention of imported malaria in France.

Prevention of malaria is based on personal vector-control measures (PVCMs) to avoid mosquito bites at night and chemoprophylaxis if justified by the risk of contracting the disease. The most effective PVCM is the use of insecticide-treated mosquito nets. The decision to prescribe chemoprophylaxis, mainly to prevent Plasmodium falciparum infection, depends on the benefit-risk ratio. Overall, the risk of contracting malaria is 1,000-fold lower during a stay in the tropical regions of Asia or the Americas than in sub-Saharan Africa. For "conventional" stays (less than one month with nights spent in urban areas) in low-risk settings in tropical Asia and America, the risk of being infected with Plasmodium parasites (≤1/100,000) is equivalent or lower than that of experiencing serious adverse effects caused by chemoprophylaxis. Preventive medication is therefore no longer recommended. By contrast, in other settings and particularly in sub-Saharan Africa, chemoprophylaxis is the most effective measure against malaria. However, it is worth noting that no single preventive measure provides full protection. Regardless of the level of risk or chemoprophylaxis-related indication, protection against mosquito bites and rapid management of febrile illness after returning from an endemic area are also critical to prevent malaria. Finally, migrants of sub-Saharan origin visiting friends and relatives in their country of origin form a high-risk group who should be recommended chemoprophylaxis in the same way as any other travelers-with a preference for the least expensive molecules (doxycycline).

Management and prevention of imported malaria in children. Update of the French guidelines.

Since the 2007 French guidelines on imported Falciparum malaria, the epidemiology, treatment, and prevention of malaria have changed considerably requiring guidelines for all Plasmodium species to be updated. Over the past decade, the incidence of imported malaria has decreased in all age groups, reflecting the decrease in the incidence of malaria in endemic areas. The rates of severe pediatric cases have increased as in adults, but fatalities are rare. The parasitological diagnosis requires a thick blood smear (or a rapid immunochromatographic test) and a thin blood film. Alternatively, a rapid antigen detection test can be paired with a thin blood film. Thrombocytopenia in children presenting with fever is highly predictive of malaria following travel to a malaria-endemic area and, when detected, malaria should be strongly considered. The first-line treatment of uncomplicated P. falciparum malaria is now an artemisinin-based combination therapy (ACT), either artemether-lumefantrine or artenimol-piperaquine, as recommended by the World Health Organization in endemic areas. Uncomplicated presentations of non-falciparum malaria should be treated either with chloroquine or ACT. The first-line treatment of severe malaria is now intravenous artesunate which is more effective than quinine in endemic areas. Quinine is restricted to cases where artesunate is contraindicated or unavailable. Prevention of malaria in pediatric travelers consists of nocturnal personal protection against mosquitoes (especially insecticide-treated nets) combined with chemoprophylaxis according to the risk level.

Four novel mutations of the coproporphyrinogen III oxidase gene.

Here we report the characterization of four novel mutations and a previously described one of the coproporphyrinogen III oxidase (CPO) gene in five Italian patients affected by Hereditary Coproporphyria (HCP). Three of the novel genetic variants are missense mutations (p.Gly242Cys; p.Leu398Pro; p.Ser245Phe) and one is a frameshift mutation (p.Gly188TrpfsX45).

[Immunization for children travelling to the tropics: neglected vaccines]. / Enfants voyageurs se rendant sous les tropiques: les vaccins négligés.

Each year hundreds of thousands of children leave France to travel to developing countries where they are exposed to infectious agents that can be prevented by vaccination. During the child's pre-travel check-up, practitioners should check that all mandatory immunizations are up-to-date and provide advice on relevant vaccines in function of the epidemiological situation at the chosen destination. However various factors hinder full compliance with this approach and some vaccines are underused. Underused vaccines are referred to as neglected vaccines. In the French vaccination schedule three vaccinations can be considered as neglected. The first is the hepatitis B vaccine that has a low coverage level in France due to strong reluctance to its use despite the fact that the virus is widespread in tropical areas. The second is pneumococcal vaccine that should be administered to all infants less than 2 years of age, especially for travel to areas where pneumonia and meningitis are frequent. The third is BCG vaccine that is now at greater risk of being neglected in child travellers because its use has been downgraded from a general requirement to a recommendation only for children at risk. A serious limitation on the use of travel vaccinations is cost that can lead families to neglect some infectious risk such as hepatitis A that is a major risk for child travellers as well as for their relatives during or after the trip and typhoid fever that is essentially an imported disease. Rabies vaccine is also underused due to its cost and to poor understanding of the risk by many practitioners and families. The purpose of this article is to underline the need to improve information and access to vaccines that are all too often neglected in child travellers.

[Vaccinations for traveler child]. / Vaccinations de l'enfant voyageur.

Each year, half a million of children leave France to travel towards countries south or east of the European Union, sometimes in poor sanitary conditions. In order to propose essential or useful immunizations for these trips, the current synthesis will allow the practitioner to insure that the routine French immunization schedule has been followed, and to complete it if needed, to protect the child according to the epidemiological situation in the visited area, to try to reduce the limitations of the immunization of the traveler child. In case of emergency, or close departure, it may be useful to follow an accelerated schedule of the last minute, and, sometimes, to immunize traveler children with a chronic disease. Informations on Internet sites useful for the knowledge of current infectious risks in the destination country are also provided.

[Children arthropod bites protective measures: insecticides and repellents]. / Protection antivectorielle de l'enfant: insecticides et insectifuges.

Vector transmitted diseases are often a serious threat for child health, especially for children traveller in tropical regions. Few arthropod borne diseases are preventable by immunization or chimioprophylaxis. Prevention of most of them is based on personal protection against arthropod bites. The evidence of its efficacy has been established by the use of impregnated bed nets, impregnated clothes with permethrin or mosquito repellent which reduced significantly child malaria morbidity and mortality in endemic countries. These personal protective measures are able to minimize arthropod bites and prevent Chikungunya infection, dengue fever and Lyme disease. The choice of a repellent among the commercialised products need to be efficacy and safety evidence based. This article propose to raise this issue and to give pragmatic recommendations, with a focus to children below 30 months who are at a high toxicological risk. Severity of these diseases allowed to use potentially toxic repellents if misused.

[Autochthonous dengue]. / La dengue autochtone.

Dengue is the arboviral disease that has massively spread in intertropical regions these past few years. The rise in imported cases of dengue and the rapid spread of the Aedes vector mosquitoes in continental France since 2004 explain the occurrence of indigenous dengue cases among the nonimmune population and points to an epidemic risk. Severe dengue cases are rare, but lethality is highest among children under 5 years of age. Like pediatricians in tropical regions, we must learn how dengue presents in metropolitan France and how it can be managed, and pay special attention to severe and potentially fatal forms. The epidemiological, pathophysiological, clinical, diagnostic, and therapeutic characteristics of dengue are presented herein.

[Fever in children returning from travel]. / Fièvre au retour de voyage chez l'enfant.

Child travelers are numerous, exposed to the risk of diseases, both infectious and noninfectious, for which practitioners often lack experience. The assessment of febrile returning child travelers is becoming more frequent and challenging. The question of previous travel should be foremost in the checklist of the interview of any febrile child traveler, because this implies a possible tropical disease such as malaria that may be life-threatening. These need to be investigated and treated effectively and rapidly. There are highly contagious infections that could pose public health risks requiring implementation of hygienic and public health measures. A detailed immunization, medical, and travel history for exposure to infectious risks using geographic, seasonal, environmental, sociocultural, and epidemiological data are needed. Along with clinical examination and elementary first-line investigations, the history should guide second-line exams, which will provide the etiology and optimal treatment in approximately 75 % of cases. The majority of children will have a cosmopolitan infection that resolves spontaneously or is simple to treat. Malaria will need urgent and specific treatment. This article describes guidance on first-line evaluation and management of febrile child travelers as recommended in France.

Insulin response to oral glucose in patients with a previous myocardial infarction and in patients with peripheral vascular disease. Hyperinsulinism and its relationships to hypertriglyceridemia and overweight.

The insulin response to an oral glucose load (100 gm.) in 127 patients with a previous myocardial infarction (MI) (six months to one year) and in 65 patients with surgically treated or arteriographically identified peripheral vascular disease (PVD) was compared with that of 89 controls after matching the three collectives for age, glucose tolerance, and per cent ideal body weight (% IBW). The insulin response was of greater magnitude in MI and PVD groups than in respective control groups also in the absence of hyperglycemia, hypertriglyceridemia, and obesity. This finding suggests that hyperinsulinism may represent an early metabolic alteration associated with the development of MI and PVD. The insulin secretion pattern was prevalently of the delayed type in association with impaired glucose tolerance and with hypertriglyceridemia but not with overweight. Correlations between serum insulin, triglyceride (TG) levels, and % IBW were also investigated. We found a strong correlation (p less than 0.001) between stimulated insulin levels and % IBW in MI patients and none in PVD patients; conversely, the correlation between serum insulin and TG levels was very high (p less than 0.001) in PVD patients and only weak (p less than 0.05) in MI patients. No correlation was found between cholesterol (CH) levels and any of the other parameters studied. According to these results, it seems likely that hyperinsulinism plays a major role as a closely associated factor to obesity in those subjects who develop an MI, whereas in PVD patients the raised insulin levels may favor lipid accumulation in the arterial intima and accelerate the progress of atherosclerosis.

Clinical and metabolic aspects of continuous ambulatory peritoneal dialysis (CAPD).

Experience with CAPD in 14 patients, treated for periods of 2-10 months, is presented. Clinical and biochemical control of uremia appeared adequate in all patients except one. Control of extracellular volume and hypertension was easier with CAPD than with intermittent peritoneal dialysis (IPD). Nine episodes of peritonitis occurred in 5 patients (one peritonitis/8 patients months). Mean protein loss was 9.7 +/- 2.7 g per day. In 6 patients on IPD oral glucose tolerance test resulted in a paradoxical rise of HGH, whereas this was not observed after 4 months of CAPD.

[Acute uncomplicated malaria treatment in children in France in 2002]. / Traitement de l'accès palustre non compliqué de l'enfant en France en 2002.

CONTEXT AND OBJECTIVES: Imported P. falciparum malaria cases are rising in France reaching 1300 estimated children in 2000. Three years after the publication of therapeutic guidelines, the Groupe de Pédiatrie Tropicale conducted an observational survey in order to describe the practice of acute uncomplicated malaria treatments in children, to identify their limits and to make proposals to improve them. METHODS: A self administrated questionnaire has been proposed to 29 pediatric wards declaring over 10 malaria cases in 2000. Questions were focused on treatment practices and monitoring of children diagnosed with acute uncomplicated malaria in 2002. RESULTS: Twenty-six services, who treated more than 700 children, responded. Twenty-two on 26 services hospitalized systematically malaria cases. Mean duration of hospitalization was 2.2 days (S.D. +/- 0.9). First line treatment was halofantrine in 22 on 26 services and mefloquine in four services. A second halofantrine dose was given systematically at day 7 in three services. No clinical cardiac effects happened. Quinine was used in perfusion only in cases of gastric intolerance. Treatment failure has never been experienced in the 22 services using halofantrine and has been experienced at least once in two on four wards using mefloquine. Relapse occurred at least once in 19 on 22 wards treating with halofantrine. DISCUSSION: Halofantrine with hospitalization is still the leading treatment of acute uncomplicated malaria in children in France. In spite of the absence of clinical cardiac incident, a second cure of halofantrine was not often used, exposing to a high rate of relapse. Mefloquine is three time more used than in 1997, in spite of its digestives side effects that can explain failures of treatment. When done, the systematic clinical and parasitological control confirms failures after mefloquine and the high incidence of relapse after one cure of halofantrine. Only used in case of severity or digestive disorders, quinine is a little less prescribed in acute uncomplicated malaria in 2001 than in 1997. CONCLUSIONS: The limitations of antimalarial drugs used in France in case of acute malaria argue for an improvement of protocols (systematic second reduced dose of halofantrine after day 7, mefloquine associated with antiemetic drug) and a systematic clinical and parasitological monitoring. As alternative, efficient combinations of antimalarial as first line treatment are needed in France.

[Counsel for traveling children]. / Conseils pour enfants voyageurs.

Consultation of child traveler has two main objectives: to assess of health risk related to the child's health status and history and also the risk related to travel environment; to counsel and prescribe preventive measure to reduce these travel health risks. The evaluation is based on physical examination and a detailed interview including personal history and information regarding the regions of proposed travel. Up to date knowledge of the epidemiology of visited sites, preventive measures and presumptive treatment is required. Essential health recommendations include, in case of exposure, prevention of malaria, arthropod borned diseases and vaccine preventable diseases. For all destinations advice regarding prevention of diarrhea, accident risks and aggravation of preexisting chronic diseases is needed. Universal primary prevention counselling is valuable for all travellers regardless of their age. In the case of children, special attention must be given to food and water hygiene, sun and heat exposure, swimming risks and transports security measures. Evaluation of risk and health education take time and often several visits are needed to complete the immunization schedule before departure.