High HIV vulnerability of ethnic minorities after a trans-Asian highway construction in remote northern Laos.

From 2004 to 2008 a new Asian highway was constructed through remote multiethnic areas of north Laos linking a low with higher HIV prevalence areas in bordering Thailand and China. We assessed the HIV vulnerability in four minority villages alongside the new road in Luang Namtha Province using structured interviews and voluntary counselling and testing (VCT) for HIV. Of 470 villagers aged 15-49 years old, 47.0% did not know any ways of HIV transmission yet 82.1% reported sexual contacts. Median age at first sex was 17.5 years. Sex of never-married 15-24 years old was associated with higher age (P = 0.002) and ethnicity (P = 0.013; Hmong odds ratio [OR] 7.27); 61.9% (86/139) used no condom at last non-cohabitant sex, especially women (OR 17.7, P < 0.001) and older villagers (P = 0.001). No HIV-infection was detected among villagers who received VCT in 2006 (924 of 933) and 2008 (538 of 1249). Nonetheless our findings reveal an alarming vulnerability for HIV among ethnic minorities alongside the new highway, and further culturally adapted prevention efforts are warranted.

[Epilepsy in Lao Popular Democratic Republic: difficult procurement of a first-line antiepileptic contributes to widening the treatment gap]. / Épilepsie au Laos : le difficile parcours d'un antiépileptique de première ligne contribue à la forte carence de traitement.

INTRODUCTION: In Laos, over 95% of people with epilepsy (PWE) do not receive a proper treatment. Traditional beliefs and practices have long explained this wide treatment gap. From 2008 to 2010 we evaluated the procurement process for phenobarbital, the leading first-line antiepileptic drug (AED) in Laos, and its availability at a national scale as a potential additional major cause of this treatment gap in Laos. METHODS: Data were drawn from several surveys conducted from 2008 to 2010: (i) semi structured interviews of key persons from the Ministry of Health and from pharmaceutical factories, wholesalers, pharmacists, neurologists, psychiatrists, and non-governmental organisations; (ii) retrospective survey of AED prescriptions in three main hospitals of Vientiane the capital city during two randomised weeks from June to August 2009; (iii) self-administered questionnaires of pediatricians regarding their knowledge about phenobarbital; (iv) a national survey of the AED availability in pharmacies and drug shops in 16/17 provinces, 16 districts and 96 villages (multistage randomised survey) in 2010 and a survey among the population in 2009. RESULTS: Phenobarbital is imported in Laos via a carefully controlled importation process either as raw material to be processed by factory N(o) 2 or in the form of tablets. The International Narcotics Control Board (Vienne) delivers a yearly quota of 25kg of raw phenobarbital to the Food and Drug department (FDA). This allows the production of 245000 tablets per year (around 671 annual adult treatments). The overall importation process for phenobarbital lasts 6months. Grade 1 pharmacists (mostly located in urban areas) and regional and district hospitals are authorized to deliver phenobarbital. The cost of phenobarbital ranged from 0.11 to 0.2US dollars/tablet per day (39 to 67US dollars per year). High cost of transportation and increased cost of phenobarbital (5- to 10-fold greater than the international market) contribute to reduce access to treatment. CONCLUSION: Needs for phenobarbital at delivery sites should be re-assessed by the health authorities based on the expected number of PWE. Improved training of health and pharmacist personnel and increased awareness of the population concerning effective long-term treatment for epilepsy are crucial to improve access of PWE to AED in Laos.

[Bacterial flora in acute exacerbations of chronic obstructive pulmonary disease (COPD) in Kunming, China]. / Flore bactérienne des exacerbations aiguës de bronchopneumopathie chronique obstructive (BPCO) à Kunming, Chine.

OBJECTIVE: Chinese recommendations for the management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) include antibiotic treatments targeting the most frequently isolated pathogens according to the severity of COPD. The study objective was to check the relevance of these recommendations in Yunnan, a Southern Chinese province. PATIENTS AND METHODS: A descriptive and analytical survey was conducted in the Kunming Medical University hospital among patients over 60 years of age, hospitalized with AECOPD, between March 2007 and June 2008. RESULTS: The 74 included patients were predominantly male (90%), with a mean age of 78.6 years, active or ex-smokers (81%), mainly with moderate (43%) or severe COPD (34%). Out of 87 AECOPD episodes, 47 (54%) yielded significant quantitative sputum cultures for S. pneumoniae (10%), P. aeruginosa (10%), H. influenzae (7%), M. catarrhalis (7%), and K. pneumoniae (7%). The positivity of sputum cultures was significantly linked with a history of smoking (P=0.002). More than half of the P. aeruginosa isolates were multidrug resistant. CONCLUSIONS: The distribution of pathogens isolated from EABPCO in Kunming corroborates published results. It does not question Chinese recommendations for first-line antibiotic therapy, but the high prevalence of P. aeruginosa and Enterobacteriaceae requires a periodic screening for acquired antibiotic resistance.

[Is oral rehydration with nasogastric tube more efficient than rehydration with spoon? Preliminary study in children with non-severe dehydration in Joseph-Raseta-Befelatanana Hospital, Madagascar]. / La réhydratation orale par sonde gastrique est-elle plus efficace que la réhydratation orale par cuillère ? Etude préliminaire chez l'enfant atteint de déshydratation non sévère à l'hôpital Joseph-Raseta-Befelatanana, Madagascar.

Since its recommendation by WHO, Oral Rehydration Solutions (ORS) contributed in reducing the rate of mortality due to acute gastroenteritis. In Madagascar, the rate of lethality imputed to gastroenteritis is about 3%. Rehydration can be performed either by using spoons which reliability is unsure because of parents' potential inobservance and child's refusal, or by nasogastric tube. The nasogastric tube may resolve these obstacles at the hospital. We realized a preliminary study to evaluate the efficacy and the safety of nasogastric tube and spoon administration of the ORS in rehydration of child with moderate post-gastroenteritis dehydration. This is an open comparative study realized in the Pediatric Unit at the Joseph-Raseta-Befelatanana Hospital from the 21 January to 21 May 2008. Main outcomes was the proportion of rehydrated children at 4 hours, other were: failure at 8 hours, duration and volume of SRO, side effects. Fifty-three children from 4-month to 4-year old among 1306 patients were recruited and forty-seven patients were included. Nine patients failed (4 children received ORS by spoon and 5 children by nasogastric tube). The use of spoon was more effective: 62.5% of the patients were rehydrated at the fourth hour versus 39.3% in nasogastric tube group (P = 0.04). Making debit constant presents difficulties in rehydration with nasogastric tube (44.4 %). Tolerance of nasogastric tube is generally good but 16.7% children get out their tube during this study. No ORS' inhalation was observed with both routes. No false passage or tube or ORS rejection was recorded in both techniques. This study shows that using spoon to rehydrate is more effective for the rehydration of moderate dehydration. The use of nasogastric tube needs more surveillance.

[Mother's educational level and children's illness severity in the emergency unit of Joseph-Raseta-Befelatanana Hospital. What kind of implications]. / Education des mères et gravité de l'état des enfants présentés aux urgences de l'hôpital Joseph-Raseta-Befelatanana, Madagascar. Quelles implications ?

The parents 'educational conditions are one of the factors of health inequalities among children. During May 2009, the parents' instruction level of children admitted at the triage unit of a Pediatric Service in Antananarivo, Madagascar was evaluated and related to the severity of their children' health status and to the mode of reference. All the surviving children (from 2 months to 15 years old) were included in this study. Patients were classified by the IMCI guideline and we analyzed the educational level of their mothers. Each patient was classified as severe illness or without severe illness, according to IMCI algorithm. The quality of referring physician was recorded: public physicians, liberal physicians, nurses, or without referral. Among 296 children, 9 (3%) died before admission, 217 (75.6%) were included. Among them, 123 (56.7%) had a severe illness and 38,2% general signs of danger. The severity (92.3 versus 54.4%; P = 0.003), the number of severe dehydration (15.4 versus 3.9%; P = 0,027) and malnutrition (15.4 versus 4.4%; P = 0.039) were related with a poor parents educational level. The referral agents were mostly liberal physicians (56.7%), public physicians (26.7%) or nurses (1.8%). Mothers with higher educational level preferred to attend liberal physicians (58 versus 41.9%; P = 0.1). The reference delay was shorter if there was a severe illness (6.41 versus 19.6 days; P < 0.000) or no medical referral (51.1 versus 24.4%; P > 0.000). Despite the fact that access to hospital care was respectful of a two-step process (85.3%), the number of patients with severe illness was high among families with low educational level. Theses results suggest to educate in priority the mother with low education, in order to recognize the general signs of danger and facilitate early first health care.

The bleach method improves the detection of pulmonary tuberculosis in Laos.

SETTING: Laos has a high prevalence of tuberculosis (TB) and a low prevalence of human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS). Mycobacterium tuberculosis culture is not yet available. Case finding is based on the microscopic detection of acid-fast bacilli (AFB) in sputum. Liquefaction and concentration using sodium hypochlorite (bleach) could improve its yield. OBJECTIVE: To assess the gain due to the bleach method and its feasibility in Laos, and to compare the classical method sputum processing (direct microscopy) and the bleach method for AFB detection over 3 consecutive months at a central site (Vientiane) and for 1 month at a peripheral site (Attapeu). RESULTS: Of 1675 sputum samples collected from 612 patients, respectively 206 (12.3%) and 275 (16.4%) were AFB-positive by the direct and bleach methods (P = 0.0007), i.e., an increase in smear positivity rate of 33.5% (95%CI 31.2-35.8). The superiority of the bleach method was confirmed, regardless of the site, the aspect of the sputum and delay before analysis. This method yielded 24 more TB patients. CONCLUSION: The bleach method, which is very easy to use, could significantly increase the yield of sputum smear microscopy for the detection of pulmonary TB in Laos.

[Two outbreaks of eosinophilic meningitis in Yunann (China) clinical, epidemiological and therapeutical issues]. / Epidémies de méningite à éosinophiles au Yunnan (Chine): aspects épidémiologiques, cliniques et thérapeutiques.

Eosinophilic meningitis is an uncommon clinical entity, which is mostly caused by Angiostrongylus cantonensis, a nematode which parasitizes rat's lungs. Humans represent a dead-end in the parasite's lifecycle and become infected by ingesting snails, slugs or transport hosts. Due to uncontrolled proliferation and circulation of snails and rats, human angiostrongyliasis has emerged in new foci in continental China. The treatment, which relies upon a combination of albendazole and corticosteroids, is still a matter of debate. In order to assess the epidemiological features of two outbreaks which occurred in Kunming, capital of the Yunnan province, 2003 and 2005, along with the clinical and treatment issues, a retro-prospective study was carried out among thirty-four clinical cases of eosinophilic meningitis. Furthermore, a parasitological survey was carried out on randomized samples of snails sold in the markets of the city On admission, all cases were found to have acute headaches and an eosinophilic pleocytosis rate > 5% in the cerebro spinal fluid (CSF). All patients reported the consumption of raw snails Pomacea canaliculata, 14 days on average before the onset of headaches (range 1-30 days). Hyperesthesia due to radiculitis was observed in 68% of the cases and the meningitis syndrome was present in 41%. The average value of blood eosinophil count in CSF and in peripheral blood was 38% and 900/ml, respectively. Two treatment schedules were used (without randomization): one with progressive doses over 4 weeks; the other with immediate high doses for 10 days with 3 sessions separated by 14-day intervals. The results were compared by the Kaplan Meier log rank test. All the cases had a favorable evolution. The analysis suggested better effectiveness and tolerance of the albendazole - dexamethasone combination used at the highest dosage, namely 20mglkg daily and 10mg daily respectively. Eosinophilic meningitis appeared to be recently emerging or re-emerging in Kunming. Deep-rooted culinary habits of eating raw food, and large amount of snails sold on local markets (about one ton per day) provide ideal conditions for the outbreak, or occurrence of this disease. According to the resdjlts of this study Chinese local authorities should be urged to improve information to the population about the risks of eating raw snails, in order to strengthen the control of both rat and snail populations and reinforce the supervision of local food markets.

Trichinellosis during pregnancy: a case control study in the Lao Peoples' Democratic Republic.

Transmission of Trichinella to humans is still a global public health concern. Although theoretically possible, vertical transmission of Trichinella has rarely been investigated. In June 2005 an outbreak of trichinellosis was reported in Udomxay province, the Northern Lao Peoples' Democratic Republic (PDR). In February and March 2006 we performed a study of all pregnant and lactating mothers and infants in the location of this outbreak to assess the possible occurrence of vertical transmission. The study used questionnaires, mother and child clinical examinations, and serology (Western blot) and, based on the results, women were classified as suspect, possible, or confirmed cases. A control group included unexposed pregnant women and their children. Among 200 women from 21 villages, 8 were confirmed positive for trichinellosis by serology; 4 of these were symptomatic. Among their children, one died in utero at 26 weeks gestation due to maternal hepatitis of unknown etiology and a second child had Trichinella-specific IgG antibodies but was clinically normal. A third child, with negative serology had an inter-ventricular cardiac communication. The remaining children did not differ from controls. Our results cannot prove that transmission of trichinellosis occurs from mother to child.

Postpartum traditions and nutrition practices among urban Lao women and their infants in Vientiane, Lao PDR.

BACKGROUND/OBJECTIVE: To assess the traditional postpartum practices, mother and child nutritional status and associated factors. SUBJECTS/METHODS: A cross-sectional study in 41 randomly selected villages on the outskirts of Vientiane capital city, Lao PDR (Laos). 300 pairs of infants (< 6 months of age) and their mothers were enrolled. Information was collected about pregnancy, delivery and traditional practices through a standardized questionnaire. Dietary intake and food frequency were estimated using the 24 h recall method, calibrated bowls and FAO food composition tables. Mothers' and infants' anthropometry was assessed and multivariate analysis performed. RESULTS: Contrasting with a high antenatal care attendance (91%) and delivery under health professional supervision (72%), a high prevalence of traditional practices was found, including exposure to hot beds of embers (97%), use of traditional herb tea as the only beverage (95%) and restricted diets (90%). Twenty-five mothers (8.3%) were underweight. Mothers had insufficient intake of calories (55.6%), lipids (67.4%), iron (92.0%), vitamins A (99.3%) and C (45%), thiamin (96.6%) and calcium (96.6%). Chewed glutinous rice was given to infants as an early (mean 34.6, 95% CI:29.3-39.8 days) complementary food by 53.7% of mothers, and was associated with stunting in 10% children (OR=1.35, 95% CI:1.04-1.75). CONCLUSION: The high prevalence of traditional postpartum restricted diets and practices, and inadequate maternal nutritional intake in urban Laos, suggest that antenatal care may be an important opportunity to improve postpartum diets.

Identification of the human paragonimiasis causative agent in Lao People's Democratic Republic.

To assess the species of human paragonimiasis in Lao People's Democratic Republic, 6 ovum samples from 6 native confirmed paragonimiasis patients were examined with polymerase chain reaction (PCR) amplifying the internal transcribed spacer 2 (ITS2). The PCR products were sequenced, and a homology search was performed using the GenBank. All 6 sequences were identical with Paragonimus heterotremus ITS2. Our work suggests that P. heterotremus may be the main etiological agent of human paragonimiasis in this locality.

Paragonimiasis and its intermediate hosts in a transmission focus in Lao People's Democratic Republic.

Human cases of paragonimiasis have been reported in Lao People's Democratic Republic from several provinces, however, detailed descriptions of a focus of transmission including parasites species and intermediate hosts are lacking. Field investigations were carried out between February and July 2004 in three neighboring villages of the province of Vientiane. Persons with chronic cough (more than three weeks) were identified during a door-to-door survey and three sputum samples were examined for Paragonimus spp. and tuberculosis on two consecutive days. Potential intermediate snail and crustacean hosts were sampled among the populations' water-contact sites and examined for metacercarial infections or cercarial shedding. Four dogs were infected with metacercaria and the species of the subsequently retrieved adult parasites were identified. 12.7% (15 cases) of all chronic cough patients (0.6% of the total population) suffered from paragonimiasis. Samples of five species of freshwater snails, two species of crabs and one species of prawn were collected from the Nam Sêt River. None of the snails were infected. Metacercariae of P. harinasutai, P. bangkokensis and P. heterotremus were found in Potamon lipkei crabs while an infection with P. westermani was observed in a Chulathelphusa brandti crab. No paragonimid metacercaria was found in the Macrobrachium dienbienphuense prawns Dang and Nguyen 1972. This study demonstrates the importance of Paragonimus spp. as an etiological agent in patients with chronic cough and suggests that similar transmission might be widespread in Lao People's Democratic Republic. We document herein the transmission of several Paragonimus species indicating that paragonimiasis is an active zoonosis in Lao People's Democratic Republic.

Review of STI and HIV epidemiological data from 1990 to 2001 in urban Burkina Faso: implications for STI and HIV control.

OBJECTIVES: To better understand the sexually transmitted infection (STI)/HIV dynamics in an urban west African setting in order to adapt STI/HIV control efforts accordingly. METHODS: Review of STI and HIV epidemiological studies performed over the past decade in Bobo-Dioulasso, the second city of Burkina Faso. Trends in STI prevalence among commercial sex workers and the general population were assessed over time through studies that used the same recruitment and laboratory diagnostic procedures. Variations in aetiologies of vaginal discharge, urethral discharge, and genital ulcers were also evaluated among patients consulting for genital infection complaints. Antenatal clinic based surveys provided data to assess HIV trend among the general population. RESULTS: We observed an important decline of classic bacterial STI such as syphilis, Neisseria gonorrhoea, Chlamydia trachomatis, and Haemophilus ducrey infections in all study groups. Trichomoniasis also declined but to a lesser extent. HIV infection followed the same trend at the same time, with a significant decline in the 15-19 year age group of pregnant women, suggesting a possible decrease of HIV incidence. Although no evidence of a causal relation can be drawn from this review, adoption of safer sex behaviour, introduction of the syndromic management (SM) approach, or higher antibiotic use may have contributed to these changes. CONCLUSIONS: Classic bacterial STI declined over the past decade in parallel with a stabilisation of HIV infection. Variations in syndromes aetiology and sexual behaviours should be monitored as part of STI surveillance in order to improve STI syndromic management algorithms and to adapt HIV/STI prevention efforts.

Early glucose and methylene blue are effective against unripe ackee apple (Blighia sapida) poisoning in mice.

The ingestion of unripe ackee fruit (Blighia sapida) is responsible for lethal epidemic encephalopathy in West Africa and the Caribbean. The treatment of ackee poisoning remains empirical and lethality was 100% in a recent epidemic in Burkina Faso. Because ackee poisoning has certain biochemical similarities to ifosfamide encephalopathy, we evaluated the efficacy of methylene blue (MB) and glucose (G), alone and in combination (MB+G) in mice, as a treatment for ackee poisoning. MB administration showed some efficacy towards early mortality (P=0.07) but not to late mortality. No deaths were observed when 8 mg/kg MB was administrated within 1h of the ackee poisoning. The treatment was ineffective if given 6h or later after poisoning. Survival in G and G+MB groups was higher than in MB group (75% and 25% respectively) (P=0.008, R=2.0, 1.14

Intrarectal pharmacokinetics of two formulations of quinine in children with falciparum malaria.

OBJECTIVE: To compare the intrarectal bioavailabilities of two parenteral formulations of quinine most available in French- (Cinchona alkaloid mixture) and English (hydrochloride salt) -speaking areas of Africa. METHODS: The pharmacokinetics of quinine was investigated in four groups of 12 children with acute Plasmodium falciparum malaria receiving 8 mg/kg quinine base every 8 h either as hydrochloride salt or Cinchona alkaloid mixture by a slow 4-h intravenous infusion or intrarectal administration. Body temperature and parasitaemia were monitored, and blood quinine concentrations were measured by means of high-performance liquid chromatography. RESULTS: At 72 h, all the children were aparasitaemic and apyretic. Quinine C(max) values were higher after intravenous infusion of the hydrochloride salt and Cinchona alkaloid mixture (6.9+/-1.9 micro g/ml and 5.2+/-1.3 micro g/ml) than after intrarectal administration (3.5+/-1.4 micro g/ml and 3.1+/-1.6 micro g/ml), but t(max) values were similar (3.6+/-1.5, 4.2+/-1.0, 4.0+/-1.9, and 4.7+/-2.0 h, respectively). Intrarectal relative bioavailabilities of hydrochloride salt solution (57%) and Cinchona alkaloid mixture (62%) were similar. CONCLUSION: Whatever the parenteral formulation of quinine, the blood concentration-time profiles of quinine were similar after intrarectal administration. Intrarectal administration of hydrochloride salt solution is a possible mode of quinine delivery in remote rural areas of Africa.

[An epidemic risk of yellow fever in Burkina Faso despite a rapid immunisation riposte: role of a multidisciplinary investigation team]. / Riposte vaccinale et persistance d'un risque épidémique de fièvre jaune dans la région de Gaoua au sud-ouest du Burkina Faso: intérêt d'une équipe pluridisciplinaire.

UNLABELLED: On October 8, 1999, one yellow fever (YF) case is confirmed in the South West of Burkina Faso by the Centre Muraz' virology unit. Epidemic extension is suspected as large movements of population are occurring due to troubles in Côte d'Ivoire nearby and as the Aedes vector is endemic in the region. On October 23, the Gaoua's Health Regional Head immunizes 1,000 people around the detected YF case, i.e. 70% of the estimated population and requests an epidemiological investigation. A multidisciplinary team (epidemiologist, entomologist, virologist) from the Centre Muraz, a medical research centre based in Bobo Dioulasso investigate in order to answer the following questions: are there any other or asymptomatic cases of YF? How far is the epidemic risk? Is a paper filter a valuable method for collecting blood samples? What benefit can be gained from a multidisciplinary team? METHOD: An epidemiological analysis of the patient, a research of asymptomatic or ignored patient is performed (Health Centre registers, interview of the population). This includes the research of people missing the immunisation campaign. Blood samples are collected through 5 ml EDTA glass tubes or through filter paper in order to measure immunoglobuline M. A classical entomological prospecting completes the investigation. RESULTS: Two possible cases are suspected in the patient's home. History of the patient's is in agreement with a local contamination. In the village 110 people missed the immunisation campaign and samples were collected in 58 people including 26 children. Among them, four (15.3%) were positive with immunoglobuline M, while there were none in the adults. Aedes Luteocephalus, a potential vector is collected through night-captures but is absent of home-water collection. Paper filter assays shows a 100% concordance with classical method. CONCLUSION: The team could determine the persistency of a yellow fever epidemic risk in the region despite a rapid and adequate immunisation riposte. Due to iterative sporadic cases and due to population movement, a routine survey of YF has to be promoted as the immune status of the population, particularly in the youth, do not protect them. Collection of blood through paper filter will greatly help the routine survey and shall be confirmed during the following investigations.

[Intrarectal administration of quinine: an early treatment for severe malaria in children?]. / Administration intrarectale de la quinine: un traitement précoce du paludisme grave de l'enfant?

Delay for treatment of severe malaria is the cause of an important childhood mortality in Africa especially in rural zone when health facilities and accessibility are scarce. Intrarectal treatment is of particular interest in children as a non aggressive, painless and easy treatment. It can be used as early treatment and could decrease the lethality of severe malaria. We recently showed the kinetic profile, the optimal regimen and the clinical efficacy of intrarectal quinine (QIR) using Quinimax (Sanofi, Gentilly France) 20 mg/kg in solution with 2 ml of water. From 1994 to 1996 two open clinical trials were performed in Niger in children (2-15 years). QIR was compared with intraveinous infusion in cerebral malaria (n = 76) and with intramuscular quinine in severe malaria (n = 57). A three daily QIR administration (20 mg/kg followed by 15 mg/kg/8 h) was used in cerebral malaria; a two daily administration in severe malaria (30 mg/kg followed by 20 mg/kg/12 h). Symptomatic treatment was associated for hyperthermia, hypoglycemia, anemia and seizures. Results. In the cerebral malaria study 58 children presented a Blantyre coma score below 3. Four children in the IR group and 9 children in the infusion group died (P > 0.05). Evolution was similar in both treatment groups: temperature clearance (< 37.5 degrees C) 39.0 +/- 15.2 h and 37.1 +/- 16.5 h; return to consciousness 34.6 +/- 12.8 h and 33.0 +/- 14.1 h; decrease to 50% of the initial parasites count: 15.5 +/- 11.5 h and 13.8 +/- 10.0 h. Residual blood quinine concentrations at 48 hours were similar 7.4 +/- 3.7 mg/l and 7.2 +/- 2.9 mg/l. In the severe malaria study, the mortality was 0 and 7.6% in the QIR and IM group respectively (P > 0.005). Evolution was similar in both treatment groups: temperature clearance (< 37.5 degrees C) 38.7 +/- 22.8 h and 38.6 +/- 22.2 h; return to consciousness 26.8 +/- 13.9 h and 27.6 +/- 9.9 h for the 16 children in coma. The evolution under QIR treatment was also similar with that described with the other quinine routes. QIR allows an efficious treatment particularly when correct infusion cannot be performed. The efficacy, the simplicity and the good tolerance of QIR are of major concern to decrease the mortality of severe malaria due to delay for treatment and to decrease the side-effects due to intramuscular administrations of quinine in Africa.

Quinine disposition in globally malnourished children with cerebral malaria.

BACKGROUND: Both malnutrition and malaria affect drug disposition and are frequent among children in the tropics. We assessed their respective influence on quinine distribution. METHODS: Forty children were divided into 4 groups: children with normal nutritional status without (group 1) or with (group 2) cerebral malaria, and malnourished children without (group 3) or with (group 4) cerebral malaria. All children received an infusion of 8 mg/kg of a combination solution of cinchona alkaloids that contained 96.1% quinine, 2.5% quinidine, 0.68% cinchonine, and 0.67% cinchonidine (corresponding to 4.7 mg/kg quinine base). The children with malaria then received repeated infusions every 8 hours for 3 days. Pharmacokinetic profiles of plasma and erythrocyte quinine were determined during the first 8 hours, together with quinine protein binding. Additional measurements of plasma quinine concentrations were used to simulate quinine concentrations profiles in children with malaria with and without malnutrition. Clinical recovery and parasitemia clearance times were determined in the children with malaria. RESULTS: Compared with control children, malaria and malnutrition increased plasma concentrations of quinine and reduced both the volume of distribution and the total plasma clearance. Simultaneously, alglycoprotein plasma concentrations and protein-bound fraction of the drug were increased. Erythrocyte quinine concentrations correlated strongly with free plasma quinine but not with the extent of parasitemia. Similar effective and nontoxic quinine concentration profiles were obtained in malaria with and without malnutrition. CONCLUSIONS: Severe global malnutrition and cerebral malaria have a similar effect on quinine pharmacokinetics in children. Moderate malnutrition does not potentiate cerebral malaria-mediated modifications of quinine disposition. These results suggest that current parenteral quinine regimens can be used, unmodified, to treat children with both malaria and malnutrition.

[Intramuscular injections in Sub-saharan African children, apropos of a frequently misunderstood pathology: the complications related to intramuscular quinine injections]. / Les injections intramusculaires chez l'enfant en afrique subsaharienne, à propos d'une pathologie souvent méconnue: les complications liées aux injections intramusculaires de quinine.

In West Africa, the incidence of poliomyelitis has decreased in the past years thanks to intensive immunization campaigns. Nowadays intramuscular injection is the main reason for paralysis of the legs in African children as well as attendance at Rehabilitation Centres. Intramuscular injection of quinine is the most frequently reported. Faced with the lack of sterile material, health workers do not rationalize the use of intramuscular injections. Although the use of the same needle has decreased, using the same syringe for many patients, with only a rapid washing between, is still commonplace Poor septic conditions and abuse of prescriptions also contribute to the transmission of severe diseases (hepatitis, malaria, syphilis, filariasis, Ebola virus, tetanus and HIV). Paralysis due to injection is often confused with poliomyelitis and health workers are often not aware of the sequelae of injection. It seems important to prevent risk related to intramuscular injection in Africa through educating health workers and the local population. Rationalization of practises, promotion of oral therapy and alternatives to intramuscular administration should be carried out. In this respect, the intrarectal administration of an injectable solution of diluted quinine--its efficiency and pharmacokinetic having been studied over the last ten years--offers interesting opportunities.

Epidemic of fatal encephalopathy in preschool children in Burkina Faso and consumption of unripe ackee (Blighia sapida) fruit.

BACKGROUND: On March 21, 1998, the Regional Health Authority of Bobo-Dioulasso, Burkina Faso, asked the Centre Muraz to investigate an unexplained outbreak of epidemic fatal encephalopathy (EFE). We aimed to identify the cause of this epidemic. METHODS: We identified cases retrospectively through review of health-service records and interviews of family members, village chiefs, and local healers. Active surveillance was started in administrative divisions within the study area in April, 1998, to identify further EFE cases. We did a case-control study of households to investigate the risk from various environmental and health factors. Blood and urine samples were collected if possible and urine dicarboxylic acid concentrations measured by gas chromatography. FINDINGS: 29 cases of EFE were identified from January to May, 1998. Estimated age-specific attack rates (2-6 years) ranged from 31 to 847 per 100,000 population (p<0.001). The most common symptoms were hypotonia, vomiting, convulsions, and coma. All children died in 2-48 h. The only factor associated with EFE was the presence of ackee trees (Blighia sapida) within 100 m of households (odds ratio 5.1 [95% CI 1.8-14.7] p=0.001). Poisoning with unripe ackee fruits was suggested by urine concentrations of dicarboxylic acids four to 200 times higher in cases (n=2) than in controls (n=3). CONCLUSION: Consumption of unripe ackee fruit probably caused this epidemic and may lead to a substantial number of unexplained deaths in preschool children in west Africa every year. Educational campaigns have the potential to prevent these deaths.

[Tolerance of quinine administered as an intrarectal solution in children in French-speaking Africa]. / Tolérance de la quinine administrée en solution intrarectale chez l'enfant en Afrique francophone.

Pharmacokinetic studies have documented the efficacy of intrarectal quinine (IRQ) for treatment of childhood malaria. As a result, this technique has gradually supplanted intramuscular injection of quinine (IMQ), a common source of complications in children. To assess the safety of this technique, outcome was routinely monitored from 1987 to 1997. This report presents immediate tolerance observed in clinical studies involving 915 children as well as two surveys conducted in Niamey, Niger on 2764 children in 1995 and on 714 children in 1997. In the second study tolerance of IRQ (n = 364) and IMQ (n = 350) was compared. Long-term tolerance was evaluated for 11 years in a single location, i.e. Morondava, Madagascar. In 1995 IRQ accounted for 19.6 p. 100 of antimalarial treatments prescribed in Niamey. In 1997, IRQ accounted for 34.5 p. 100 of quinine prescriptions (excluding infusions) written in medical centers and 65.7 p. 100 in the Pediatric Department B of the hospital in Niamey. Overall tolerance was good, thus confirming previous clinical studies. No major and/or irreversible complication was observed. Early rejection (12.9 p. 100), intestinal transit problems (4.3 p. 100), and watery stools (12.9 p. 100) were the most common problems. In contrast, IMQ led to residual pain (3.1 p. 100), local inflammation (3.1 p. 100), abscess (0.6 p. 100), and lower extremity disability (0.3 p. 100). The precautions for use, e.g. proper dilution, and staff training requirements are reviewed in the discussion.