Prioritising pathogens for the management of severe febrile patients to improve clinical care in low- and middle-income countries.

BACKGROUND: Severe febrile illness without a known source (SFWS) is a challenge for clinicians when deciding how to manage a patient, particularly given the wide spectrum of potential aetiologies that contribute to fever. These infections are difficult to distinguish clinically, and accurate diagnosis requires a plethora of diagnostics including blood cultures, imaging techniques, molecular or serological tests, and more. When laboratory services are available, a limited test menu hinders clinical decision-making and antimicrobial stewardship, leading to empiric treatment and suboptimal patient outcomes. To specifically address SFWS, this work aimed to identify priority pathogens for a globally applicable panel for fever causing pathogens. METHOD: A pragmatic two-pronged approach combining currently available scientific data in an analytical hierarchy process and systematically gathered expert input, was designed to address the lack of comprehensive global aetiology data. The expert re-ranked list was then further adapted for a specific use case to focus on community acquired infections in whole blood specimens. The resulting list was further analysed to address different geographical regions (Asia, Africa, and Latin America), and Cohen kappa scores of agreement were calculated. RESULTS: The expert ranked prioritized pathogen list generated as part of this two-pronged approach included typhoidal Salmonella, Plasmodium species and Mycobacterium tuberculosis as the top 3 pathogens. This pathogen list was then further adapted for the SFWS use case to develop a final pathogen list to inform product development. Subsequent analysis comparing the relevance of the SFWS pathogen list to multiple populations and geographical regions showed that the SFWS prioritized list had considerable utility across Africa and Asia, but less so for Latin America. In addition, the list showed high levels of agreement across different patient sub-populations, but lower relevance for neonates and symptomatic HIV patients. CONCLUSION: This work highlighted once again the challenges of prioritising in global health, but it also shows that taking a two-pronged approach, combining available prevalence data with expert input, can result in a broadly applicable priority list. This comprehensive utility is particularly important in the context of product development, where a sufficient market size is essential to achieve a sustainable commercialized diagnostic product to address SFWS.

Quantifying the incidence of severe-febrile-illness hospital admissions in sub-Saharan Africa.

Severe-febrile-illness (SFI) is a common cause of morbidity and mortality across sub-Saharan Africa (SSA). The burden of SFI in SSA is currently unknown and its estimation is fraught with challenges. This is due to a lack of diagnostic capacity for SFI in SSA, and thus a dearth of baseline data on the underlying etiology of SFI cases and scant SFI-specific causative-agent prevalence data. To highlight the public health significance of SFI in SSA, we developed a Bayesian model to quantify the incidence of SFI hospital admissions in SSA. Our estimates indicate a mean population-weighted SFI-inpatient-admission incidence rate of 18.4 (6.8-31.1, 68% CrI) per 1000 people for the year 2014, across all ages within areas of SSA with stable Plasmodium falciparum transmission. We further estimated a total of 16,200,337 (5,993,249-27,321,779, 68% CrI) SFI hospital admissions. This analysis reveals the significant burden of SFI in hospitals in SSA, but also highlights the paucity of pathogen-specific prevalence and incidence data for SFI in SSA. Future improvements in pathogen-specific diagnostics for causative agents of SFI will increase the abundance of SFI-specific prevalence and incidence data, aid future estimations of SFI burden, and enable clinicians to identify SFI-specific pathogens, administer appropriate treatment and management, and facilitate appropriate antibiotic use.

Ebola Virus Disease Outbreak in Isiro, Democratic Republic of the Congo, 2012: Signs and Symptoms, Management and Outcomes.

Data collected during the 2012 Ebola virus disease (EVD) epidemic in the Democratic Republic of the Congo were analysed for clinical signs, symptoms and case fatality of EVD caused by Bundibugyo virus (BDBV), establishment of differential diagnoses, description of medical treatment and evaluation of the quality of clinical documentation. In a quantitative observational prospective study, global epidemiological data from 52 patients (34 patients within the community, 18 patients treated in the Ebola Treatment Centre) were entered anonymously into a database, subsequently matched and analysed. Relevant findings include an over-representation of females among community EVD cases (85.3%) and of community EVD cases in the age group of 15-54 years (82.4%). All ETC patients had fever (55.6% of all 18 ETC patients during their hospital stay) or self-reported fever (88.2% upon admission) at some point of time during their illness. Major symptoms of ETC patients during hospital stay included asthenia (82.4%), anorexia (82.4%), myalgia (70.6%), sore throat/difficulty swallowing (70.6%), arthralgia (76.5%) and nausea (70.6%). Gastrointestinal signs and symptoms (nausea, diarrhoea, vomiting) (76.4%) as well as general pain (94.1%) were frequent in ETC patients. The median duration of EVD was 18 days, while the mean incubation period was 11.3 days. Differential diagnosis of EVD included malaria (28.3%), intestinal parasitosis (10.9%), and infectious syndrome (10.9%). There was also an important variation in clinical evolvement. Quality of documentation was adversely affected by the way patient file contents were transferred from inside to outside the high-risk zone, entailing a mean mismatch value of 27.3% between patient file contents inside vs. outside the high-risk zone. This study adds further description of EVD (frequently non-specific signs and symptoms, non frequent bleeding, a long incubation period, long duration of disease) and emphasizes the need for improving clinical monitoring and documentation in EVD outbreak settings.

A call to action to enhance filovirus disease outbreak preparedness and response.

The frequency and magnitude of recognized and declared filovirus-disease outbreaks have increased in recent years, while pathogenic filoviruses are potentially ubiquitous throughout sub-Saharan Africa. Meanwhile, the efficiency and effectiveness of filovirus-disease outbreak preparedness and response efforts are currently limited by inherent challenges and persistent shortcomings. This paper delineates some of these challenges and shortcomings and provides a proposal for enhancing future filovirus-disease outbreak preparedness and response. The proposal serves as a call for prompt action by the organizations that comprise filovirus-disease outbreak response teams, namely, Ministries of Health of outbreak-prone countries, the World Health Organization, Médecins Sans Frontières, the Centers for Disease Control and Prevention-Atlanta, and others.

Clinical documentation and data transfer from Ebola and Marburg virus disease wards in outbreak settings: health care workers' experiences and preferences.

Understanding human filovirus hemorrhagic fever (FHF) clinical manifestations and evaluating treatment strategies require the collection of clinical data in outbreak settings, where clinical documentation has been limited. Currently, no consensus among filovirus outbreak-response organisations guides best practice for clinical documentation and data transfer. Semi-structured interviews were conducted with health care workers (HCWs) involved in FHF outbreaks in sub-Saharan Africa, and with HCWs experienced in documenting and transferring data from high-risk areas (isolation wards or biosafety level 4 laboratories). Methods for data documentation and transfer were identified, described in detail and categorised by requirement for electricity and ranked by interviewee preference. Some methods involve removing paperwork and other objects from the filovirus disease ward without disinfection. We believe that if done properly, these methods are reasonably safe for certain settings. However, alternative methods avoiding the removal of objects, or involving the removal of paperwork or objects after non-damaging disinfection, are available. These methods are not only safer, they are also perceived as safer and likely more acceptable to health workers and members of the community. The use of standardised clinical forms is overdue. Experiments with by sunlight disinfection should continue, and non-damaging disinfection of impregnated paper, suitable tablet computers and underwater cameras should be evaluated under field conditions.

Monitoring HIV viral load in resource limited settings: still a matter of debate?

INTRODUCTION: Consequences of lack of viral monitoring in predicting the effects of development of HIV drug resistance mutations during HAART in resource-limited settings (RLS) is still a matter of debate. DESIGN: To assess, among HIV+ patients receiving their first-line HAART, prevalence of virological failure and genotypic resistance mutations pattern in a Médécins Sans Frontières/Ministry of Health programme in Busia District (Kenya). METHODS: Patients with HAART treatment for ≥12 months were eligible for the study and those with HIV-RNA ≥5000 copies/ml underwent genotypic study. Total HIV-1 RNA from Dried Blood Spots was extracted using Nuclisens method. RESULTS: 926 patients were included. Among 274 (29.6%) patients with detectable viral load, 55 (5.9%) experienced treatment failure (viral load >5.000 copies/ml); 61.8% were female and 10 (18.2%) had clinical failure. Median CD4 cell count was 116 cell/mm3 (IQR: 54-189). Median HIV-RNA was 32,000 copies/ml (IQR: 11000-68000). Eighteen out of 55 (33%) samples could be sequenced on PR and RT genes, with resistance associated mutations (RAMs) in 15 out of 18 samples (83%). Among patients carrying RAMs, 12/15 (81%) harboured RAMs associated to thymidine analogues (TAMs). All of them (100%) showed M184V resistance associated mutation to lamivudine as well as NNRTI's RAMS. CONCLUSIONS: Virological failure rate in resource-limited settings are similar to those observed in developed countries. Resistance mutation patterns were concordant with HAART received by failing patients. Long term detectable viral load confers greater probability of developing resistance and as a consequence, making difficult to find out a cost-effective subsequent treatment regimen.

Evaluation of clinical and immunological markers for predicting virological failure in a HIV/AIDS treatment cohort in Busia, Kenya.

BACKGROUND: In resource-limited settings where viral load (VL) monitoring is scarce or unavailable, clinicians must use immunological and clinical criteria to define HIV virological treatment failure. This study examined the performance of World Health Organization (WHO) clinical and immunological failure criteria in predicting virological failure in HIV patients receiving antiretroviral therapy (ART). METHODS: In a HIV/AIDS program in Busia District Hospital, Kenya, a retrospective, cross-sectional cohort analysis was performed in April 2008 for all adult patients (>18 years old) on ART for ≥12 months, treatment-naive at ART start, attending the clinic at least once in last 6 months, and who had given informed consent. Treatment failure was assessed per WHO clinical (disease stage 3 or 4) and immunological (CD4 cell count) criteria, and compared with virological failure (VL >5,000 copies/mL). RESULTS: Of 926 patients, 123 (13.3%) had clinically defined treatment failure, 53 (5.7%) immunologically defined failure, and 55 (6.0%) virological failure. Sensitivity, specificity, positive predictive value, and negative predictive value of both clinical and immunological criteria (combined) in predicting virological failure were 36.4%, 83.5%, 12.3%, and 95.4%, respectively. CONCLUSIONS: In this analysis, clinical and immunological criteria were found to perform relatively poorly in predicting virological failure of ART. VL monitoring and new algorithms for assessing clinical or immunological treatment failure, as well as improved adherence strategies, are required in ART programs in resource-limited settings.

Clinical manifestations and case management of Ebola haemorrhagic fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007-2008.

A confirmed Ebola haemorrhagic fever (EHF) outbreak in Bundibugyo, Uganda, November 2007-February 2008, was caused by a putative new species (Bundibugyo ebolavirus). It included 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR = 25%). Study objectives are to describe clinical manifestations and case management for 26 hospitalised laboratory-confirmed EHF patients. Clinical findings are congruous with previously reported EHF infections. The most frequently experienced symptoms were non-bloody diarrhoea (81%), severe headache (81%), and asthenia (77%). Seven patients reported or were observed with haemorrhagic symptoms, six of whom died. Ebola care remains difficult due to the resource-poor setting of outbreaks and the infection-control procedures required. However, quality data collection is essential to evaluate case definitions and therapeutic interventions, and needs improvement in future epidemics. Organizations usually involved in EHF case management have a particular responsibility in this respect.

Ebola haemorrhagic fever outbreak in Masindi District, Uganda: outbreak description and lessons learned.

BACKGROUND: Ebola haemorrhagic fever (EHF) is infamous for its high case-fatality proportion (CFP) and the ease with which it spreads among contacts of the diseased. We describe the course of the EHF outbreak in Masindi, Uganda, in the year 2000, and report on response activities. METHODS: We analysed surveillance records, hospital statistics, and our own observations during response activities. We used Fisher's exact tests for differences in proportions, t-tests for differences in means, and logistic regression for multivariable analysis. RESULTS: The response to the outbreak consisted of surveillance, case management, logistics and public mobilisation. Twenty-six EHF cases (24 laboratory confirmed, two probable) occurred between October 21st and December 22nd, 2000. CFP was 69% (18/26). Nosocomial transmission to the index case occurred in Lacor hospital in Gulu, outside the Ebola ward. After returning home to Masindi district the index case became the origin of a transmission chain within her own extended family (18 further cases), from index family members to health care workers (HCWs, 6 cases), and from HCWs to their household contacts (1 case). Five out of six occupational cases of EHF in HCWs occurred after the introduction of barrier nursing, probably due to breaches of barrier nursing principles. CFP was initially very high (76%) but decreased (20%) due to better case management after reinforcing the response team. The mobilisation of the community for the response efforts was challenging at the beginning, when fear, panic and mistrust had to be countered by the response team. CONCLUSIONS: Large scale transmission in the community beyond the index family was prevented by early case identification and isolation as well as quarantine imposed by the community. The high number of occupational EHF after implementing barrier nursing points at the need to strengthen training and supervision of local HCWs. The difference in CFP before and after reinforcing the response team together with observations on the ward suggest a critical role for intensive supportive treatment. Collecting high quality clinical data is a priority for future outbreaks in order to identify the best possible FHF treatment regime under field conditions.

Filovirus hemorrhagic fever outbreak case management: a review of current and future treatment options.

Testing an innovative therapy for filovirus hemorrhagic fever (FHF) in an outbreak setting may be years away. Moreover, beyond anecdotal evidence, little is known about best practice for outbreak case management. Currently, Médecins Sans Frontières and others provide FHF patients with basic supportive treatment. We describe and discuss treatment possibilities, challenges, and potential next steps for FHF outbreak case management. More comprehensive supportive treatment, including vital sign monitoring, intensive care components, and goal-directed interventions may contribute to improved clinical outcome; the feasibility and effectiveness of this more comprehensive supportive treatment should be assessed. Our outlined summary may assist future FHF outbreak case management teams to create collaborative platforms and develop relevant treatment protocols aimed at improving clinical outcome.

Effectiveness and safety of liposomal amphotericin B for visceral leishmaniasis under routine program conditions in Bihar, India.

We evaluated, through the prospective monitoring of 251 patients at Sadar Hospital in Bihar, India, the effectiveness and safety of 20 mg/kg body weight of liposomal amphotericin B for the treatment of visceral leishmaniasis. The treatment success rates for the intention-to-treat, per protocol, and intention-to-treat worse-case scenario analyses were 98.8%, 99.6%, and 81.3%, respectively. Nearly one-half of patients experienced mild adverse events, but only 1% developed serious but non-life-threatening lips swelling. The lost to follow-up rate was 17.5%. Our findings indicate that the 20 mg/kg body weight treatment dosage is effective and safe under routine program conditions. Given that the exorbitant cost of liposomal amphotericin B is a barrier to its widespread use, we recommend further study to monitor and evaluate a lowered dosage and a shorter treatment course.

Factors associated with Marburg hemorrhagic fever: analysis of patient data from Uige, Angola.

BACKGROUND: Reliable on-site polymerase chain reaction (PCR) testing for Marburg hemorrhagic fever (MHF) is not always available. Therefore, clinicians triage patients on the basis of presenting symptoms and contact history. Using patient data collected in Uige, Angola, in 2005, we assessed the sensitivity and specificity of these factors to evaluate the validity of World Health Organization (WHO)-recommended case definitions for MHF. METHODS: Multivariable logistic regression was used to identify independent predictors of PCR confirmation of MHF. A data-derived algorithm was developed to obtain new MHF case definitions with improved sensitivity and specificity. RESULTS: A MHF case definition comprising (1) an epidemiological link or (2) the combination of myalgia or arthralgia and any hemorrhage could potentially serve as an alternative to current case definitions. Our data-derived case definitions maintained the sensitivity and improved the specificity of current WHO-recommended case definitions. CONCLUSIONS: Continued efforts to improve clinical documentation during filovirus outbreaks would aid in the refinement of case definitions and facilitate outbreak control.

Infection control during filoviral hemorrhagic fever outbreaks: preferences of community members and health workers in Masindi, Uganda.

Interviews were conducted with health workers and community members in Masindi, Uganda on improving the acceptability of infection control measures used during an Ebola outbreak. Measures that promote cultural sensitivity and transparency of control activities were preferred and should be employed in future control efforts. We suggest assessing the practicality of body bags with viewing windows, and face shields with or without chin protectors, in future outbreaks.

Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières.

BACKGROUND: Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness. METHODOLOGY: From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999-2002); Olopa, Guatemala (2003-2006); Entre Ríos, Bolivia (2002-2006); and Sucre, Bolivia (2005-2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs. RESULTS: Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population. CONCLUSIONS: These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed.

Field evaluation of a rapid immunochromatographic assay for detection of Trypanosoma cruzi infection by use of whole blood.

Laboratory and clinical diagnostic classification of seropositive individuals, followed by treatment and supportive therapy, is an established component of Chagas' disease control in areas where this disease is endemic. However, most Chagas' disease patients live in remote areas where neither equipped laboratories nor skilled human resources are widely available. Employing a rapid diagnostic test (RDT), when using whole blood samples, is the best option for Chagas' disease control. A high sensitivity and specificity for the Chagas Stat-Pak RDT (Chembio Diagnostic Systems, Inc., Medford, NY) has been reported for assays using serum and plasma, but its validity for the detection of antibodies to Trypanosoma cruzi infection in whole blood is unknown. This cross-sectional study measured the sensitivity and specificity of the Chagas Stat-Pak with whole blood, using conventional serological assays for comparison. The interobserver reliability in the interpretation of the Chagas Stat-Pak results and "ease-of-use" criterion needed to perform the Chagas Stat-Pak and conventional assays were also measured. The Chagas Stat-Pak yielded a high specificity (99.0%, 95% confidence interval [CI] = 98.4 to 99.4%) but a relatively low sensitivity (93.4%, 95% CI = 87.4 to 97.1%). The interobserver reliability was excellent (kappa [n = 1,913] = 0.999, P < 0.0001), and the quantified ease-of-use criterion suggested that the RDT is simple to perform. Despite the attributes of the Chagas Stat-Pak, it is not an ideal diagnostic test for the population investigated in the present study due to its relatively low sensitivity and high cost. The RDT manufacturer is called upon to improve the test if the international community hopes to make progress in controlling Chagas infections in areas where this disease is endemic.

Tratamiento etiológico, efectos secundarios y seroconversión en pacientes con infección por el Trypanosoma cruzi. Experiencia de dos proyectos, en Honduras y Guatemala, América Central / No disponible

Entre 1999 y 2006, en Yoro, Honduras, y Olopa, Guatemala, Médicos sin Fronteras implementó dos proyectos en los que se evaluó la seguridad y eficacia del benznidazol en el tratamiento de niños menores de 15 años de edad con infección chagásica crónica reciente. En Honduras fueron tamizados 24.471 niños, de los cuales 232 fueron confirmados positivos (seroprevalencia del 0,93%). Se trataron con benznidazol 231 casos, con seguimiento semanal y evaluaciones serológicas postratamiento. El 88,2% presentaron seroconversión a los 18 meses y el 93,9% a los tres años. Se detectaron efectos adversos en un 50,2% de los pacientes tratados, siendo la gran mayoría leves, con necesidad de suspensión del tratamiento sólo en tres casos. Los más comunes fueron los gastrointestinales (53,4%), seguidos de los cutáneos (25,9%) y neurológicos (20,7%).En Guatemala fueron tamizados 8.927 niños, resultando positivos 124 (prevalencia 1,5%).Sus controles serológicos postratamiento aún están siendo procesados. Los efectos secundarios aparecieron en un 50,8% de los 124 pacientes, siendo más frecuentes los gastrointestinales (25,7%) y cutáneos (25,7%), seguidos de los neurológicos (22,8%). Los resultados de estas dos experiencias evidencian que en Centroamérica el diagnóstico y tratamiento de la infección chagásica crónica reciente son factibles, necesarios para la población infectada y éticamente incuestionables (AU)

Between 1999 and 2006 in Yoro, Honduras, and Olopa, Guatemala, Mèdecins Sans Frontières implemented two projects assessing the safety and efficacy of benznidazol for the treatment of children under fifteen of age with an early chronic phase of Trypanosomacruzi infection. In Honduras 24,471 children were screened, of which 232 were confirmed positive (seroprevalence of 0.93%). 231 patients were treated with weekly follow up and post-treatment serological follow-up. 88.2% of the patients seroconverted at 18 month sand 93.9% at 3 years after treatment. Side effects were present in 50.2% of the patients, but most of these were mild and only three patients had to stop their treatment. The most frequent were gastrointestinals (53.4%), followed by cutaneous (25.9%) and neurological(20.7%) manifestations. In Guatemala 8,927 children were screened, resulting in 124positive cases (prevalence 1.5%). Side effects were reported in 50.8% of the patients and the most common were gastrointestinal (25.7%) and cutaneous (25.7%), followed by neurological (22.8%) manifestations. In Guatemala the verification of the post-treatment seroconversion is currently ongoing. The results of these two treatment experiences show that in Central America both the diagnostic and treatment of T.cruzi infection are feasible, needed and ethically unquestionable (AU)

The Medecins Sans Frontieres intervention in the Marburg hemorrhagic fever epidemic, Uige, Angola, 2005. I. Lessons learned in the hospital.

When the epidemic of Marburg hemorrhagic fever occurred in Uige, Angola, during 2005, the international response included systems of case detection and isolation, community education, the burial of the dead, and disinfection. However, despite large investments of staff and money by the organizations involved, only a fraction of the reported number of cases were isolated, and many cases were detected only after death. This article describes the response of Medecins Sans Frontieres Spain within the provincial hospital in Uige, as well as the lessons they learned during the epidemic. Diagnosis, management of patients, and infection control activities in the hospital are discussed. To improve the acceptability of the response to the host community, psychological and cultural factors need to be considered at all stages of planning and implementation in the isolation ward. More interventional medical care may not only improve survival but also improve acceptability.

The Medecins Sans Frontieres intervention in the Marburg hemorrhagic fever epidemic, Uige, Angola, 2005. II. lessons learned in the community.

From 27 March 2005 onwards, the independent humanitarian medical aid agency Medecins Sans Frontieres, together with the World Health Organization, the Angolan Ministry of Health, and others, responded to the Marburg hemorrhagic fever (MHF) outbreak in Uige, Angola, to contain the epidemic and care for those infected. This response included community epidemiological surveillance, clinical assessment and isolation of patients with MHF, safe burials and disinfection, home-based risk reduction, peripheral health facility support, psychosocial support, and information and education campaigns. Lessons were learned during the implementation of each outbreak control component, and the subsequent modifications of protocols and strategies are discussed. Similar to what was seen in previous filovirus hemorrhagic fever outbreaks, the containment of the MHF epidemic depended on the collaboration of the affected community. Actively involving all stakeholders from the start of the outbreak response is crucial.

Evidence basis for antimalarial policy change in Sierra Leone: five in vivo efficacy studies of chloroquine, sulphadoxine-pyrimethamine and amodiaquine.

OBJECTIVES: To provide nationally relevant information on the antimalarial efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) in Sierra Leone, with a view to updating antimalarial policy in the country. METHODS: Between October 2002 and May 2003, standard WHO methodology for in vivo efficacy assessment was used in five sites to study the therapeutic response of 6-59 months old uncomplicated Plasmodium falciparum malaria cases treated with CQ (n = 247), SP (n = 353) or AQ (n = 434). Follow-up was of 28 days, with polymerase chain reaction genotyping to distinguish late recrudescences from re-infections. RESULTS: Overall 85.3% of patients reached an analysable endpoint. CQ failure proportions were very high, ranging from 39.5% (95% CI: 25.0-55.6) in Kabala to 78.8% (65.3-88.9) in Kailahun. Early failures under CQ were frequent. SP efficacy was also disappointing, with failure from 23.2% (13.9-34.9) in Kabala to 46.1% (35.4-57.0) in Kailahun. AQ resistance was more moderate, ranging from 5.4% (1.8-12.1) in Makeni to 29.8% (20.3-40.8) in Kailahun, with almost no early failures. AQ also provided more rapid fever and parasite clearance. CONCLUSION: In a consensus meeting organized by the Ministry of Health and Sanitation, and based on these findings, artesunate (AS) + AQ and artemether-lumefantrine (Coartemtrade mark) were identified as the only options to rapidly replace CQ. The choice fell on AS + AQ because of expected high efficacy, lower cost in a blister presentation, and the absence of safety data on artemether-lumefantrine in pregnancy. Donor support is required to support this policy change. Throughout Africa, as SP resistance increases, these two regimens are probably the only options available while newer combinations are developed. Efficacy studies should focus on testing AQ and AS + AQ.