Should mortality data for the elderly be collected routinely in emergencies? The practical challenges of age-disaggregated surveillance systems.

Data on the elderly are rarely collected in humanitarian emergencies. During a refugee crisis in South Sudan, Médecins Sans Frontières developed a prospective mortality surveillance system collecting data for those aged ≥50 years and found that the elderly were dying at five times the rate of those aged 5-49 years. Practical and ethical issues arose. Were reported ages accurate? Since no baseline exists, what does the mortality rate mean? Should programmatic changes be made without evidence that these would reduce the elderly mortality rate? We outline issues to be addressed to enable informed decisions on response to elderly populations in emergency settings.

Accuracy of five algorithms to diagnose gambiense human African trypanosomiasis.

BACKGROUND: Algorithms to diagnose gambiense human African trypanosomiasis (HAT, sleeping sickness) are often complex due to the unsatisfactory sensitivity and/or specificity of available tests, and typically include a screening (serological), confirmation (parasitological) and staging component. There is insufficient evidence on the relative accuracy of these algorithms. This paper presents estimates of the accuracy of five algorithms used by past Médecins Sans Frontières programmes in the Republic of Congo, Southern Sudan and Uganda. METHODOLOGY AND PRINCIPAL FINDINGS: The sequence of tests in each algorithm was programmed into a probabilistic model, informed by distributions of the sensitivity, specificity and staging accuracy of each test, constructed based on a literature review. The accuracy of algorithms was estimated in a baseline scenario and in a worst-case scenario introducing various near worst-case assumptions. In the baseline scenario, sensitivity was estimated as 85-90% in all but one algorithm, with specificity above 99.9% except for the Republic of Congo, where CATT serology was used as independent confirmation test: here, positive predictive value (PPV) was estimated at <50% in realistic active screening prevalence scenarios. Furthermore, most algorithms misclassified about one third of true stage 1 cases as stage 2, and about 10% of true stage 2 cases as stage 1. In the worst-case scenario, sensitivity was 75-90% and PPV no more than 75% at 1% prevalence, with about half of stage 1 cases misclassified as stage 2. CONCLUSIONS: Published evidence on the accuracy of widely used tests is scanty. Algorithms should carefully weigh the use of serology alone for confirmation, and could enhance sensitivity through serological suspect follow-up and repeat parasitology. Better evidence on the frequency of low-parasitaemia infections is needed. Simulation studies should guide the tailoring of algorithms to specific scenarios of HAT prevalence and availability of control tools.

Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial.

BACKGROUND: Human African trypanosomiasis (HAT; sleeping sickness) caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are toxic, ineffective, or impractical. We assessed the efficacy and safety of nifurtimox-eflornithine combination therapy (NECT) for second-stage disease compared with the standard eflornithine regimen. METHODS: A multicentre, randomised, open-label, active control, phase III, non-inferiority trial was done at four HAT treatment centres in the Republic of the Congo and the Democratic Republic of the Congo. Patients aged 15 years or older with confirmed second-stage T b gambiense infection were randomly assigned by computer-generated randomisation sequence to receive intravenous eflornithine (400 mg/kg per day, every 6 h; n=144) for 14 days or intravenous eflornithine (400 mg/kg per day, every 12 h) for 7 days with oral nifurtimox (15 mg/kg per day, every 8 h) for 10 days (NECT; n=143). The primary endpoint was cure (defined as absence of trypanosomes in body fluids and a leucocyte count

Nifurtimox-eflornithine combination therapy for second-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Congo.

BACKGROUND: Human African trypanosomiasis caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are either highly toxic or impracticable in field conditions. We compared the efficacy and safety of the nifurtimox-eflornithine drug combination with the standard eflornithine regimen for the treatment of second-stage disease. METHODS: A randomized, open-label, active-control, phase III clinical trial comparing 2 arms was conducted at the Sleeping Sickness Treatment Center, which was run by Medecins Sans Frontieres, in Nkayi, Bouenza Province, Republic of Congo. Patients were screened for inclusion and randomly assigned to receive eflornithine alone (400 mg/kg per day given intravenously every 6 h for 14 days) or eflornithine (400 mg/kg per day given intravenously every 12 h for 7 days) plus nifurtimox (15 mg/kg per day given orally every 8 h for 10 days). Patients were observed for 18 months. The study's outcomes were cure and adverse events attributable to treatment. RESULTS: A total of 103 patients with second-stage disease were enrolled. Cure rates were 94.1% for the eflornithine group and 96.2% for the nifurtimox-eflornithine group. Drug reactions were frequent in both arms, and severe reactions affected 25.5% of patients in the eflornithine group and 9.6% of those in the nifurtimox-eflornithine group, resulting in 2 and 1 treatment suspensions, respectively. There was 1 death in the eflornithine arm and no deaths in the nifurtimox-eflornithine arm. CONCLUSIONS: The nifurtimox-eflornithine combination appears to be a promising first-line therapy for second-stage sleeping sickness. If our findings are corroborated by ongoing findings from additional sites (a multicenter extension of this study), the new nifurtimox-eflornithine combination therapy will mark a major and multifaceted advance over current therapies.

Treatment outcomes and risk factors for relapse in patients with early-stage human African trypanosomiasis (HAT) in the Republic of the Congo.

OBJECTIVE: In 2002-03, the Republic of the Congo increased the threshold separating stage 1 and 2 cases of human African trypanosomiasis (HAT) from a cerebrospinal fluid (CSF) white cell count of 5 cells/mm(3) to 10 cells/mm(3). We aimed to assess whether the increased threshold of 10 cells/mm(3) is a safe indicator of stage 2 disease. METHODS: We assessed patients treated for stage 1 HAT caused by Trypanosoma brucei gambiense in the Republic of the Congo between April 2001 and April 2005. Patients with 0-10 cells/mm(3) in CSF were classed as stage 1 and treated with pentamidine. Patients with CSF of > 10 cells/mm(3) were classed as stage 2 and treated with either melarsoprol or eflornithine. We did a retrospective analysis of all patients treated after the September 2002 increase in threshold for classification of HAT disease stage 2, and who were eligible for at least 1 year of follow-up. Primary outcome was survival without death or relapse within 1 year of discharge. Risk factors for treatment failure, in particular CSF white cell count on diagnosis, were assessed. FINDINGS: Between September 2002 to April 2004, 692 patients eligible for our analysis were treated with pentamidine. All were discharged alive. Relapse rate was 5% (n = 33). The only identified risk factor for relapse was a CSF white cell count of 6-10 cells/mm(3) rather than 0-5 cells/mm(3) (adjusted hazard ratio 3.27 (95% confidence interval, 1.52-7.01); P = 0.002). CONCLUSION: A threshold of 5 white cells/mm(3) in CSF is safer than 10 cells/mm(3) to determine stage 2 HAT and reduce risk of relapse.

Melarsoprol versus eflornithine for treating late-stage Gambian trypanosomiasis in the Republic of the Congo.

OBJECTIVE: To compare the effectiveness of melarsoprol and eflornithine in treating late-stage Gambian trypanosomiasis in the Republic of the Congo. METHODS: We analysed the outcomes of death during treatment and relapse within 1 year of discharge for 288 patients treated with eflornithine, 311 patients treated with the standard melarsoprol regimen and 62 patients treated with a short-course (10-day) melarsoprol regimen between April 2001 and April 2005. FINDINGS: A total of 1.7% (5/288) of patients treated with eflornithine died compared with 4.8% (15/311) of those treated with standard melarsoprol and 6.5% (4/62) of those treated with short-course melarsoprol. Patients treated with eflornithine tended to be younger and were more likely to have trypanosomes or higher white blood cell counts in their cerebrospinal fluid. The cumulated incidence of relapse among patients who attended at least one follow-up visit 1 year after discharge was 8.1% (11/136) for those treated with eflornithine, 14% (36/258) for those treated with standard melarsoprol and 15.5% (9/58) for those treated with shortcourse melarsoprol. In a multivariate analysis, when compared with eflornithine, standard melarsoprol was found to be a risk factor for both death (odds ratio (OR) = 2.87; 95% confidence interval (CI) = 1.03-8.00) and relapse (hazard ratio (HR) = 2.47; 95% CI = 1.22-5.03); when compared with eflornithine, short-course melarsoprol was also found to be a risk factor for death (OR = 3.90; 95% CI = 1.02-14.98) and relapse (HR = 6.65; 95% CI = 2.61-16.94). CONCLUSION: The effectiveness of melarsoprol treatment appears to have diminished. Eflornithine seems to be a better first-line therapy for treating late-stage Gambian trypanosomiasis in the Republic of the Congo.

Using indirect methods to understand the impact of forced migration on long-term under-five mortality.

Despite the large numbers of displaced persons and the often-lengthy periods of displacement, little is known about the impact of forced migration on long-term under-five mortality. This paper looks at the Brass Method (and adaptations of this method) and the Preceding Birth Technique in combination with a classification of women by their migration and reproductive histories, in order to study the impact of forced migration on under-five mortality. Data came from the Demography of Forced Migration Project, a study on mortality, fertility and violence in the refugee and host populations of Arua District, Uganda and Yei River District, Sudan. Results indicate that women who did not migrate in a situation of conflict and women who repatriated before the age of 15, had children with the highest under-five mortality rates compared with women who were currently refugees and women who repatriated after the age of 15.

Traumatic events and symptoms of post-traumatic stress disorder amongst Sudanese nationals, refugees and Ugandans in the West Nile.

OBJECTIVES: To compare the incidence of traumatic events and its association with symptoms of post-traumatic stress disorder in three population groups in northern Uganda and southern Sudan. METHODS: Household and individual level data collected through a single-round cross-sectional demographic survey. SETTING: The sub-counties of Yivu, Odupi and Midia in the northern Ugandan district of Arua and of Otogo in Yei River district in southern Sudan. PARTICIPANTS: Residents of these Ugandan and Sudanese sub-counties were categorized on the basis of citizenship and refugee status (i.e. as Ugandan nationals, Sudanese nationals or Sudanese refugees). The random sample population consisted of 3,323 adults (mean age: 30 years; 75% female) from 1,831 national and refugee households. RESULTS: Sudanese refugees reported the highest number of violent events experienced or witnessed ever and in the past one year . Witnessing of traumatic events, ever and in the past year , significantly predicted PTSD in surveyed population. Sex, age, education and occupation were also significantly associated with the development of PTSD symptoms. The population prevalence of PTSD was estimated to be 48% for Sudanese stayees, 46% for Sudanese refugees and 18% for Ugandan nationals. CONCLUSIONS: Symptoms of PTSD in war-affected Sudanese populations can be partly explained by traumatic event exposures. The high prevalence of violence and symptoms of PTSD in refugee populations highlight the need for better protection and security in refugee settlements. Humanitarian agencies must consider the provision of mental health services for populations affected by war and forced migration.

Psychological trauma and evidence for enhanced vulnerability for posttraumatic stress disorder through previous trauma among West Nile refugees.

BACKGROUND: Political instability and the civil war in Southern Sudan have resulted in numerous atrocities, mass violence, and forced migration for vast parts of the civilian population in the West Nile region. High exposure to traumatic experiences has been particularly prominent in the Ugandan and Sudanese of the West Nile Region, representing an indication of the psychological strain posed by years of armed conflict. METHODS: In this study the impact of traumatic events on the prevalence and severity of posttraumatic stress disorder (PTSD) in a random sample of 3.339 Ugandan nationals, Sudanese nationals, and Sudanese refugees (1.831 households) of the West Nile region is assessed. RESULTS: Results show a positive correlation between the number of traumatic events and the number of endorsed PTSD symptoms. Of the 58 respondents who experienced the greatest number of traumatizing experiences, all reported symptoms which met the DSM-IV criteria for PTSD. CONCLUSIONS: There is a clear dose-effect relationship between traumatic exposure and PTSD in the studied populations with high levels of traumatic events. In this context, it is probable that any individual could develop PTSD regardless of other risk-factors once the trauma load reaches a certain threshold.

A comparison of narrative exposure therapy, supportive counseling, and psychoeducation for treating posttraumatic stress disorder in an african refugee settlement.

Little is known about the usefulness of psychotherapeutic approaches for traumatized refugees who continue to live in dangerous conditions. Narrative exposure therapy (NET) is a short-term approach based on cognitive-behavioral therapy and testimony therapy. The efficacy of narrative exposure therapy was evaluated in a randomized controlled trial. Sudanese refugees living in a Ugandan refugee settlement (N = 43) who were diagnosed as suffering from posttraumatic stress disorder (PTSD) either received 4 sessions of NET, 4 sessions of supportive counseling (SC), or psychoeducation (PE) completed in 1 session. One year after treatment, only 29% of the NET participants but 79% of the SC group and 80% of the PE group still fulfilled PTSD criteria. These results indicate that NET is a promising approach for the treatment of PTSD for refugees living in unsafe conditions.

Mortality among displaced former UNITA members and their families in Angola: a retrospective cluster survey.

OBJECTIVE: To measure retrospectively mortality among a previously inaccessible population of former UNITA members and their families displaced within Angola, before and after their arrival in resettlement camps after ceasefire of 4 April 2002. DESIGN: Three stage cluster sampling for interviews. Recall period for mortality assessment was from 21 June 2001 to 15-31 August 2002. SETTING: Eleven resettlement camps over four provinces of Angola (Bié, Cuando Cubango, Huila, and Malange) housing 149 000 former UNITA members and their families. PARTICIPANTS: 900 consenting family heads of households, or most senior household members, corresponding to an intended sample size of 4500 individuals. MAIN OUTCOME MEASURES: Crude mortality and proportional mortality, overall and by period (monthly, and before and after arrival in camps). RESULTS: Final sample included 6599 people. The 390 deaths reported during the recall period corresponded to an average crude mortality of 1.5/10 000/day (95% confidence interval 1.3 to 1.8), and, among children under 5 years old, to 4.1/10 000/day (3.3 to 5.2). Monthly crude mortality rose gradually to a peak in March 2002 and remained above emergency thresholds thereafter. Malnutrition was the leading cause of death (34%), followed by fever or malaria (24%) and war or violence (18%). Most war victims and people who had disappeared were women and children. CONCLUSIONS: This population of displaced Angolans experienced global and child mortality greatly in excess of normal levels, both before and after the 2002 ceasefire. Malnutrition deaths reflect the extent of the food crisis affecting this population. Timely humanitarian assistance must be made available to all populations in such conflicts.