In vitro susceptibility of 120 strains of Neisseria gonorrhoeae isolated in Kyrghyzstan.

BACKGROUND: The World Health Organization has established a worldwide program for gonococcal antimicrobial surveillance, but so far no data on gonococcal susceptibility in Central Asia are available. GOAL: The need for biological data on the susceptibility of Neisseria gonorrhoeae in Kyrghyzstan, to enable adaptation of the national treatment protocol for gonococcal infections, led Médecins Sans Frontières and Epicentre to conduct a survey in collaboration with the Alfred Fournier Institute in Paris and the health authorities in Bishkek. STUDY DESIGN: In vitro susceptibility of N gonorrhoeae strains was determined with use of the reference agar-plate dilution technique. RESULTS: Results for 11 antibiotics tested on 120 strains of gonococci showed a low proportion (11.7%) of penicillinase-producing N gonorrhoeae and high proportions of intermediate or resistant strains to the majority of the antibiotics tested, including fluoroquinolones (>or=25% of strains resistant). All the strains were susceptible to spectinomycin, and only two strains had decreased susceptibility to cefixime. CONCLUSION: The therapeutic choices available in Kyrghyzstan appear to be limited to cephalosporins and spectinomycin

Risk factors for death in hospitalized dysentery patients in Rwanda.

To evaluate the management of severe dysentery cases in in-patient facilities during an epidemic of Shigella dysenteriae type 1 (Sd1), and to identify the factors associated with the risk of death, we conducted a prospective cohort study in 10 Rwandese hospitals between September and December 1994. Data were obtained from 849 cases admitted to hospitals with diarrhoea and visible blood in stools. The proportion of patients with persistent bloody diarrhoea was 51.0% at treatment day 3 and 27.9% at treatment day 5. At discharge, 79.9% had improved or were cured. The case fatality ratio was 13.2%, higher for patients treated with nalidixic acid than for those treated with ciprofloxacin (12.2% vs. 2.2%, RR = 5.80, 95% CI = 0.83-40.72). In a logistic regression model three risk factors were significantly associated with an increased risk of death during hospitalization: severe dehydration on admission (adjusted OR = 2.79, 95% CI = 1.46-5.33), age over 50 (adjusted OR vs. 5-49 age group = 3.22, 95% CI = 1.70-6.11) and prescription of nalidixic acid (adjusted OR vs. ciprofloxacin = 8.66, 95% CI = 1.08-69.67). Those results were consistent with reported high levels of resistance of Sd1 to the commonest antibiotics, including nalidixic acid. Patients belonging to groups with a higher risk of dying should be given special medical attention and supportive care. In areas of high resistance to nalidixic acid, severe cases of dysentery should be treated with fluoroquinolones in order to reduce the mortality associated with these epidemics

Adherence to the combination of sulphadoxine-pyrimethamine and artesunate in the Maheba refugee settlement, Zambia.

Artemisinin-based combination therapy (ACT) is one strategy recommended to increase cure rates in malaria and to contain resistance to Plasmodium falciparum. In the Maheba refugee settlement, children aged 5 years or younger with a confirmed diagnosis of uncomplicated falciparum malaria are treated with the combination of sulphadoxine-pyrimethamine (1 day) and artesunate (3 days). To measure treatment adherence, home visits were carried out the day after the last treatment dose. Patients who had any treatment dose left were considered certainly non-adherent. Other patients' classification was based on the answers to the questionnaire: patients whose caretakers stated the child had received the treatment regimen exactly as prescribed were considered probably adherent; all other patients were considered probably non-adherent. Reasons for non-adherence were assessed. We found 21.2% (95% CI [15.0-28.4]) of the patients to be certainly non-adherent, 39.4% (95% CI [31.6-47.6]) probably non-adherent, and 39.4% (95% CI [31.6-47.6]) probably adherent. Insufficient explanation by the dispenser was identified as an important reason for non-adherence. When considering the use of ACT, the issue of patient adherence remains challenging. However, it should not be used as an argument against the introduction of ACT. For these treatment regimens to remain efficacious on a long-term basis, specific and locally adapted strategies need to be implemented to ensure completion of the treatment

Availability and affordability of treatment for Human African Trypanosomiasis.

Human African Trypanosomiasis (HAT) is a re-emerging disease whose usual treatments are becoming less efficient because of the increasing parasite resistance. Availability of HAT drugs is poor and their production in danger because of technical, ecological and economic constraints. In view of this dramatic situation, a network involving experts from NGOs, WHO and pharmaceutical producers was commissioned with updating estimates of need for each HAT drug for the coming years; negotiations with potential producers of new drugs such as eflornithine; securing sustainable manufacturing of existing drugs; clinical research into new combinations of these drugs for first and second-line treatments; centralizing drug purchases and their distribution through a unique non-profit entity; and addressing regulatory and legal issues concerning new drugs

Death rates from malaria epidemics, Burundi and Ethiopia.

Death rates exceeded emergency thresholds at 4 sites during epidemics of Plasmodium falciparum malaria in Burundi (2000-2001) and in Ethiopia (2003-2004). Deaths likely from malaria ranged from 1,000 to 8,900, depending on site, and accounted for 52% to 78% of total deaths. Earlier detection of malaria and better case management are needed

Screening an in house alkaloids library using Voltage-Sensor Probes for new modulators of voltage-gated sodium channels

Voltage-gated sodium channels (Nav) are molecular targets of clinically used drugs for treatments of various diseases (epilepsy, chronic pain, cardiac arrhythmia…) and also of numerous animal and plant neurotoxins. The development of easy-to-use screening assays for searching new ligands from chemicals libraries, animal venoms or plant extracts represents a challenge of a great interest to generate therapeutic hits. Here, we used the mammalian GH3B6 pituitary cell line, which constitutively expresses three different neuronal Nav channel isoforms (Nav1.2, Nav1.3 and Nav1.6), to identify novel compounds of pharmacological interest from a library of in-house vegetal alkaloids. The screening is based on a method using Voltage-Sensor Probes (VSPs) that we adapted to detect both activators and blockers of Nav channels. Over the 84 pure alkaloids or plant extracts that were screened, 17 increased the VSP signal. They operated as gating modifier, showing an action mechanism similar to that of batrachotoxin (BTX), known to strongly inhibit Nav channel inactivation. The remaining 67 plant products were assessed for their potency to inhibit BTX-induced VSP signal. We further selected 11 alkaloids as efficient Nav channels inhibitors. We focused our attention on two structural analogs belonging to the aporphine family, liriodenine and oxostephanine, which differ only by a methoxy group. Whereas liriodenine has been already described as a Nav channels blocker, oxostephanine has not been yet documented as an ion channel modulator. In conclusion, the novel VSPs-based screening assay we developed is a suitable method to challenge the discovery and to assess the activity of novel ligands on Nav channels

Foci of Schistosomiasis mekongi, Northern Cambodia: II. Distribution of infection and morbidity.

In the province of Kracheh, in Northern Cambodia, a baseline epidemiological survey on Schistosoma mekongi was conducted along the Mekong River between December 1994 and April 1995. The results of household surveys of highly affected villages of the East and the West bank of the river and of school surveys in 20 primary schools are presented. In household surveys 1396 people were examined. An overall prevalence of infection of 49.3% was detected by a single stool examination with the Kato-Katz technique. The overall intensity of infection was 118.2 eggs per gram of stool (epg). There was no difference between the population of the east and west shore of the Mekong for prevalence (P = 0.3) or intensity (P = 0.9) of infection. Severe morbidity was very frequent. Hepatomegaly of the left lobe was detected in 48.7% of the population. Splenomegaly was seen in 26.8% of the study participants. Visible diverted circulation was found in 7.2% of the population, and ascites in 0.1%. Significantly more hepatomegaly (P = 0.001), splenomegaly (P = 0. 001) and patients with diverted circulation (P = 0.001) were present on the west bank of the Mekong. The age group of 10-14 years was most affected. The prevalence of infection in this group was 71.8% and 71.9% in the population of the West and East of the Mekong, respectively. The intensity of infection was 172.4 and 194.2 epg on the West and the East bank, respectively. In the peak age group hepatomegaly reached a prevalence of 88.1% on the west and 82.8% on the east bank. In the 20 schools 2391 children aged 6-16 years were examined. The overall prevalence of infection was 40.0%, ranging from 7.7% to 72.9% per school. The overalls mean intensity of infection was 110.1 epg (range by school: 26.7-187.5 epg). Both prevalence (P = 0.001) and intensity of infection (P = 0.001) were significantly higher in schools on the east side of the Mekong. Hepatomegaly (55.2%), splenomegaly (23.6%), diverted circulation (4. 1%), ascites (0.5%), reported blood (26.7%) and mucus (24.3%) were very frequent. Hepatomegaly (P = 0.001), splenomegaly (P = 0.001), diverted circulation (P = 0.001) and blood in stool (P = 0.001) were significantly more frequent in schools of the east side of the Mekong. Boys suffered more frequently from splenomegaly (P = 0.05), ascites (P = 0.05) and bloody stools (P = 0.004) than girls. No difference in sex was found for the prevalence and intensity of infection and prevalence of hepatomegaly. On the school level prevalence and intensity of infection were highly associated (r = 0. 93, P = 0.0001). The intensity of infection was significantly associated only with the prevalence of hepatomegaly (r = 0.44, P = 0. 05) and blood in stool (r = 0.40, P = 0.02). This comprehensive epidemiological study documents for the first time the public health importance of schistosomiasis mekongi in the Province of Kracheh, Northern Cambodia and points at key epidemiological features of this schistosome species, in particular the high level of morbidity associated with infection