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

Self-consistent Coulomb picture of an electron-electron bilayer system

In this work we implement the self-consistent Thomas-Fermi approach and a local conductivity model to an electron-electron bilayer system. The presence of an incompressible strip, originating from screening calculations at the top (or bottom) layer is considered as a source of an external potential fluctuation to the bottom (or top) layer. This essentially yields modifications to both screening properties and the magneto-transport quantities. The effect of the temperature, inter-layer distance and density mismatch on the density and the potential fluctuations are investigated. It is observed that the existence of the incompressible strips plays an important role simply due to their poor screening properties on both screening and the magneto-resistance (MR) properties. Here we also report and interpret the observed MR Hysteresis within our model.Comment: 12 pages, 12 figures, submitted to PR

High mortality associated with an outbreak of hepatitis E among displaced persons in Darfur, Sudan

BACKGROUND: Hepatitis E virus (HEV) causes acute onset of jaundice and a high case-fatality ratio in pregnant women. We provide a clinical description of hospitalized case patients and assess the specific impact on pregnant women during a large epidemic of HEV infection in a displaced population in Mornay camp (78,800 inhabitants), western Darfur, Sudan. METHODS: We reviewed hospital records. A sample of 20 clinical cases underwent laboratory confirmation. These patients were tested for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody to HEV (serum) and for amplification of the HEV genome (serum and stool). We performed a cross-sectional survey in the community to determine the attack rate and case-fatality ratio in pregnant women. RESULTS: Over 6 months, 253 HEV cases were recorded at the hospital, of which 61 (24.1%) were in pregnant women. A total of 72 cases (39.1% of those for whom clinical records were available) had a diagnosis of hepatic encephalopathy. Of the 45 who died (case-fatality ratio, 17.8%), 19 were pregnant women (specific case-fatality ratio, 31.1%). Acute hepatitis E was confirmed in 95% (19/20) of cases sampled; 18 case-patients were positive for IgG (optical density ratio > or =3), for IgM (optical density ratio >2 ), or for both, whereas 1 was negative for IgG and IgM but positive for HEV RNA in serum. The survey identified 220 jaundiced women among the 1133 pregnant women recorded over 3 months (attack rate, 19.4%). A total of 18 deaths were recorded among these jaundiced pregnant women (specific case-fatality ratio, 8.2%). CONCLUSIONS: This large epidemic of HEV infection illustrates the dramatic impact of this disease on pregnant women. Timely interventions and a vaccine are urgently needed to prevent mortality in this special group

A Large Outbreak of Hepatitis E Among a Displaced Population in Darfur, Sudan, 2004: The Role of Water Treatment Methods.

BACKGROUND: The conflict in Darfur, Sudan, was responsible for the displacement of 1.8 million civilians. We investigated a large outbreak of hepatitis E virus (HEV) infection in Mornay camp (78,800 inhabitants) in western Darfur. METHODS: To describe the outbreak, we used clinical and demographic information from cases recorded at the camp between 26 July and 31 December 2004. We conducted a case-cohort study and a retrospective cohort study to identify risk factors for clinical and asymptomatic hepatitis E, respectively. We collected stool and serum samples from animals and performed a bacteriological analysis of water samples. Human samples were tested for immunoglobulin G and immunoglobulin M antibody to HEV (for serum samples) and for amplification of the HEV genome (for serum and stool samples). RESULTS: In 6 months, 2621 hepatitis E cases were recorded (attack rate, 3.3%), with a case-fatality rate of 1.7% (45 deaths, 19 of which involved were pregnant women). Risk factors for clinical HEV infection included age of 15-45 years (odds ratio, 2.13; 95% confidence interval, 1.02-4.46) and drinking chlorinated surface water (odds ratio, 2.49; 95% confidence interval, 1.22-5.08). Both factors were also suggestive of increased risk for asymptomatic HEV infection, although this was not found to be statistically significant. HEV RNA was positively identified in serum samples obtained from 2 donkeys. No bacteria were identified from any sample of chlorinated water tested. CONCLUSIONS: Current recommendations to ensure a safe water supply may have been insufficient to inactivate HEV and control this epidemic. This research highlights the need to evaluate current water treatment methods and to identify alternative solutions adapted to complex emergencies

Trends in malaria morbidity following the introduction of artesunate plus amodiaquine combination in M'lomp village dispensary, south-western Senegal

BACKGROUND: In Thailand, South Africa and Zanzibar, a decrease in malaria morbidity was observed following the introduction of artemisinin-based combination therapy (ACT). In Senegal, therapeutic trials supervised the in vivo efficacy of artesunate plus amodiaquine from 1999 to 2005 at the M'lomp village dispensary. The trends in malaria morbidity in this village were evaluated from 2000 to 2002. METHODS: Each year, between July and December inclusive, fevers treated with antimalarials and slide-proven, uncomplicated malaria cases were collected from dispensary health records. Data were also collected in 1998, just prior to ACT introduction. Pearson's chi square tests and Student tests were used to compare two percentages or two means respectively (alpha = 0.05). RESULTS: Between 1998 and 2002, the total number of fevers treated with antimalarials and their repetitiveness progressively decreased: From 2824 to 945 fevers and from 17.6% to 9.7% (RR1998-2002 = 0.55; [0.44-0.69]; p < 0.0001) respectively. Considering uncomplicated malaria cases only, a decrease was observed in their total number between 2001 and 2002, from 953 to 570 cases. The incidence rate and repetitiveness also decreased. The incidence rate fell from 46.1% in 2001 to 37.5% in 2002 (p < 0.0001) and the repetitiveness decreased from 13.0% in 2000 to 6.6% in 2002 (RR2000-2002 = 0.51; [0.35-0.72]; p = 0.0001). CONCLUSION: The percentage of uncomplicated malaria cases treated with ACT increased, from 18.9% in 2000 to 64.0% in 2002, making it tempting to conclude an impact on malaria morbidity. Nonetheless, the decline in incidence rate of uncomplicated malaria was slight and a lower recorded rainfall was reported in 2002 which could also explain this decline. The context in which ACT is introduced affects the impact on malaria morbidity. In M'lomp, in contrast to studies in Thailand, South Africa and Zanzibar, ACT coverage of malaria cases was low and no vector control measure was deployed. Moreover, the malaria transmission level is higher. In sub-Saharan countries, in order to optimize the impact on malaria morbidity, ACT deployment must be supported, on the one hand, by a strengthening of public health system to ensure a high ACT coverage and, on the other hand, by others measures, such vector control measures

Different methodological approaches to the assessment of in vivo efficacy of three artemisinin-based combination antimalarial treatments for the treatment of uncomplicated falciparum malaria in African children.

BACKGROUND: Use of different methods for assessing the efficacy of artemisinin-based combination antimalarial treatments (ACTs) will result in different estimates being reported, with implications for changes in treatment policy. METHODS: Data from different in vivo studies of ACT treatment of uncomplicated falciparum malaria were combined in a single database. Efficacy at day 28 corrected by PCR genotyping was estimated using four methods. In the first two methods, failure rates were calculated as proportions with either (1a) reinfections excluded from the analysis (standard WHO per-protocol analysis) or (1b) reinfections considered as treatment successes. In the second two methods, failure rates were estimated using the Kaplan-Meier product limit formula using either (2a) WHO (2001) definitions of failure, or (2b) failure defined using parasitological criteria only. RESULTS: Data analysed represented 2926 patients from 17 studies in nine African countries. Three ACTs were studied: artesunate-amodiaquine (AS+AQ, N = 1702), artesunate-sulphadoxine-pyrimethamine (AS+SP, N = 706) and artemether-lumefantrine (AL, N = 518).Using method (1a), the day 28 failure rates ranged from 0% to 39.3% for AS+AQ treatment, from 1.0% to 33.3% for AS+SP treatment and from 0% to 3.3% for AL treatment. The median [range] difference in point estimates between method 1a (reference) and the others were: (i) method 1b = 1.3% [0 to 24.8], (ii) method 2a = 1.1% [0 to 21.5], and (iii) method 2b = 0% [-38 to 19.3].The standard per-protocol method (1a) tended to overestimate the risk of failure when compared to alternative methods using the same endpoint definitions (methods 1b and 2a). It either overestimated or underestimated the risk when endpoints based on parasitological rather than clinical criteria were applied. The standard method was also associated with a 34% reduction in the number of patients evaluated compared to the number of patients enrolled. Only 2% of the sample size was lost when failures were classified on the first day of parasite recurrence and survival analytical methods were used. CONCLUSION: The primary purpose of an in vivo study should be to provide a precise estimate of the risk of antimalarial treatment failure due to drug resistance. Use of survival analysis is the most appropriate way to estimate failure rates with parasitological recurrence classified as treatment failure on the day it occurs

A Decade Later, How Much of Rwanda's Musculoskeletal Impairment Is Caused by the War in 1994 and by Related Violence?

BACKGROUND: In 1994 there was a horrific genocide in Rwanda following years of tension, resulting in the murder of at least 800,000 people. Although many people were injured in addition to those killed, no attempt has been made to assess the lasting burden of physical injuries related to these events. The aim of this study was to estimate the current burden of musculoskeletal impairment (MSI) attributable to the 1994 war and related violence. METHODOLOGY/PRINCIPAL FINDINGS: A national cross-sectional survey of MSI was conducted in Rwanda. 105 clusters of 80 people were selected through probability proportionate to size sampling. Households within clusters were selected through compact segment sampling. Enumerated people answered a seven-question screening test to assess whether they might have an MSI. Those who were classed as potential cases in the screening test were examined and interviewed by a physiotherapist, using a standard protocol that recorded the site, nature, cause, and severity of the MSI. People with MSI due to trauma were asked whether this trauma occurred during the 1990-1994 war or during the episodes that preceded or followed this war. Out of 8,368 people enumerated, 6,757 were available for screening and examination (80.8%). 352 people were diagnosed with an MSI (prevalence=5.2%, 95% CI=4.5-5.9%). 106 cases of MSI (30.6%) were classified as resulting from trauma, based on self-report and the physiotherapist's assessment. Of these, 14 people (13.2%) reported that their trauma-related MSI occurred during the 1990-1994 war, and a further 7 (6.6%) that their trauma-related MSI occurred during the violent episodes that preceded and followed the war, giving an overall prevalence of trauma-related MSI related to the 1990-1994 war of 0.3% (95% CI=0.2-0.4%). CONCLUSIONS/SIGNIFICANCE: A decade on, the overall prevalence of MSI was relatively high in Rwanda but few cases appeared to be the result of the 1994 war or related violence

Chikungunya risk assessment for europe: recommendations for action

Since March 2005, 255 000 cases of chikungunya fever are estimated to have occurred on the island of Réunion, a French overseas department in the Indian Ocean [1]. An huge increase in estimated cases occurred at the end of December 2005, culminating in an estimated peak incidence of more than 40 000 cases in week 5 of 2006 [2]. Since then, the estimated weekly incidence trend is downwards, although there have been an estimated 3000 new cases per week since week 13 of 2006. In total, 213 deaths have been linked to the disease [1]. In Mayotte, the nearby French territorial collectivity, 5834 cases have been notified [3]. Chikungunya cases have also been reported on other islands in the Indian Ocean, and imported cases have been confirmed in several European countrie

Why don't health workers prescribe ACT? A qualitative study of factors affecting the prescription of artemether-lumefantrine

BACKGROUND: Kenya recently changed its antimalarial drug policy to a specific artemisinin-based combination therapy (ACT), artemether-lumefantrine (AL). New national guidelines on the diagnosis, treatment and prevention were developed and disseminated to health workers together with in-service training. METHODS: Between January and March 2007, 36 in-depth interviews were conducted in five rural districts with health workers who attended in-service training and were non-adherent to the new guidelines. A further 20 interviews were undertaken with training facilitators and members of District Health Management Teams (DHMTs) to explore reasons underlying health workers' non-adherence. RESULTS: Health workers generally perceived AL as being tolerable and efficacious as compared to amodiaquine and sulphadoxine-pyremethamine. However, a number of key reasons for non-adherence were identified. Insufficient supply of AL was a major issue and hence fears of stock outs and concern about AL costs was an impediment to AL prescription. Training messages that contradicted the recommended guidelines also led to health worker non-adherence, compounded by a lack of follow-up supervision. In addition, the availability of non-recommended antimalarials such as amodiaquine caused prescription confusion. Some health workers and DHMT members maintained that shortage of staff had resulted in increased patient caseload affecting the delivery of the desirable quality of care and adherence to guidelines. CONCLUSION: The introduction of free efficacious ACTs in the public health sector in Kenya and other countries has major potential public health benefits for Africa. These may not be realized if provider prescription practices do not conform to the recommended treatment guidelines. It is essential that high quality training, drug supply and supervision work synergistically to ensure appropriate case management