Understanding and Improving Malaria Diagnosis in Health Facilities in Dar es Salaam, Tanzania

In Tanzania, as in most settings of sub-Saharan Africa, malaria is the first reported cause of attendance in health facilities. The National Bureau of Statistics estimates that a total of 16 million cases and 100,000 deaths (mainly in children) are due to malaria each year. In Dar es Salaam, the main city, approximately 3 million attendances are recorded, of which about one third are due to fever, mostly considered as presumptive malaria. Recent data show that transmission intensity is much lower in urban settings than in rural lowland areas. This is especially true for Dar es Salaam where only a small fraction of all fever episodes in children and adults are actually associated with Plasmodium parasitaemia. Clinical presentation of malaria is largely unspecific. No reliable clinical predictor that allows including or excluding the diagnosis of malaria has been identified. In this context, and in the absence of diagnostic test, WHO recommended in the past all fever episodes to be treated with antimalarials. Such blanket treatment leads first to substantial over-treatment with malaria drugs (in Dar es Salaam up to 95% of all treatments are unnecessary) and second to increased risk of missing alternative diagnoses with potentially fatal outcome. To address this issue of high public health relevance, we undertook a project called IMALDIA (Improving Malaria Diagnosis) aimed at improving the management of febrile patients in health facilities in Dar es Salaam, mainly through the implementation of Rapid Diagnostic Tests for malaria (mRDT). The project had 3 major components: (1) Evaluating the safety of withholding antimalarials in febrile children with a negative mRDT living in a moderate and a highly endemic area (2) Introducing laboratory diagnosis for malaria in the routine management of fever cases, using mRDT. The focus of this operational research was to document how feasible and effective the introduction of these tests is in the context of the routine management of fever cases. (3) Understanding the aetiologies of fever cases in children by screening a group of 1000 children with detailed clinical assessments and a range of laboratory tests in order to better identify the diversity of the causes of fever in small children living in an urban and a rural area. The overall aim of the IMALDIA project was to improve the diagnostic approach and management of fever cases in health facilities in Dar es Salaam, contribute to a more efficient and effective health sector, and help Tanzania on its way to reducing infant and child mortality.In a first step, we assessed the diagnostic performance of mRDT when used by health workers in routine practice. For this purpose, a quality assurance system both at central and peripheral level was set up. This system did not detect major problem and showed that the final result of mRDT by health workers was reliable. Summary X The purpose of the second step was to better estimate the pre-test probability of malaria in populations targeted by mRDT (febrile patients of all age groups attending a health facility of any type). To this end we undertook a systematic review of the studies giving the proportion of patients with associated P. falciparum parasitemia (PFPf) in Sub-Saharan Africa. We found that the median PFPf was 35%, and that it had decreased by half when comparing the period before with the period after the year 2000 (44% versus 22%). This relatively low pre-test probability nowadays is another reason to implement mRDT in Africa. In Dar es Salaam the PFPf was very low (below 10%) hence it was even more urgent to start using a reliable malaria test. Microscopy was available in almost all public health facilities of the city but its performance was extremely low, with an overall sensitivity of 71% and a specificity of only 47%. On the request of several Tanzanian stake-holders, in particular clinicians working routinely with patients, we assessed the safety of withholding antimalarials in children under five years with a negative malaria test. We did not observe any complication or death due to a missed diagnosis of malaria in our cohort of 1000 children, of which 60% were negative by mRDT. We concluded that the strategy of withholding antimalarials in negative children is safe and does not expose the child to an increased risk. The results of the systematic review coupled with the findings of the safety study led us to question the appropriateness of the previous WHO recommendation of treating all fevers with antimalarials in children less than five years living in highly endemic areas. WHO has now changed its policy, confirming that the IMALDIA findings were very relevant to the changed situation of many African countries, including Tanzania. The core of this thesis, and the main objective of the IMALDIA project, was to investigate the feasibility and value of implementing mRDT in the management of fever episodes in an urban malaria setting. Using 2 different designs and 2 independent data sources, we found a three quarter reduction in antimalarial consumption following RDT implementation. This massive reduction was due to the higher accuracy of routine mRDT compared to routine microscopy (that led to a dramatic reduction in the number of positive patients) and to the confidence of health workers in mRDT results (the proportion of negative patients treated with antimalarials dropped from 53% to 7%). The impact was maintained up to the end of the observation period (18 months). Not surprisingly, mRDT implementation increased the prescription of antibiotics by 50% and unfortunately did not have a major impact on the quality of the medical consultation. We took the opportunity of our near-to-program implementation of mRDT to perform a cost-saving analysis in a real situation and in a setting representative of many moderate endemic places in Africa. The conclusion was that costs can be saved on drugs, from both the provider and from the client’s perspective. For this reason, the overall expenditure for the patient was lower in health facilities using mRDT (by 0.31 USD per patient). However, the overall expenditure for the health Summary XI system was higher (by 1.31 USD per patient) when using mRDT instead of routine microscopy, mainly because of the relatively high price of the device. The aim of the last study was to explore the other causes of fever (beside malaria), in order to generate evidence for a revision of the existing clinical decision-charts for the management of patients, in particular the Integrated Management of Childhood Illness (IMCI). Half of the fever episodes in children were due to acute respiratory infections (ARI), of which 2/3 were probably of viral origin. Only 5% of all ARI were documented pneumonia. Gastroenteritis contributed to 9% of all fevers, of which at least 1/3 were due to a virus. In 1/5 of the children, no aetiology of high probability could be found but most of them recovered without treatment. Most of the children with acute fever thus do not need to receive an antibiotic. Based on these findings, we proposed a limited series of modifications to the IMCI chart and concluded that new point-of-care laboratory tests for the main infectious diseases are urgently needed. In conclusion, the IMALDIA project provided a deep insight into many aspects of the implementation of mRDT in near-to-programme conditions in Tanzania. Our findings show that the introduction of mRDT is safe, feasible and useful for the routine management of fever cases in all age groups and at all levels of the health system. Implementation at large scale will require flexibility on the part of the health care provider in order to be able to change his/her behaviour and a strong commitment of all persons involved. As malaria diagnosis is only one aspect of the management of patients presenting with fever, this will not solve all obstacles for making a proper differential diagnosis and prescribing the appropriate treatment for fever episodes. To really improve the quality of care it will be essential to develop new improved guidelines for clinicians. These decision charts should be based on the new available evidence and could include novel point-of-care tests for the key diseases, once these become availabl

The Human Brain Encodes Event Frequencies While Forming Subjective Beliefs

To make adaptive choices, humans need to estimate the probability of future events. Based on a Bayesian approach, it is assumed that probabilities are inferred by combining a priori, potentially subjective, knowledge with factual observations, but the precise neurobiological mechanism remains unknown. Here, we study whether neural encoding centers on subjective posterior probabilities, and data merely lead to updates of posteriors, or whether objective data are encoded separately alongside subjective knowledge. During fMRI, young adults acquired prior knowledge regarding uncertain events, repeatedly observed evidence in the form of stimuli, and estimated event probabilities. Participants combined prior knowledge with factual evidence using Bayesian principles. Expected reward inferred from prior knowledge was encoded in striatum. BOLD response in specific nodes of the default mode network (angular gyri, posterior cingulate, and medial prefrontal cortex) encoded the actual frequency of stimuli, unaffected by prior knowledge. In this network, activity increased with frequencies and thus reflected the accumulation of evidence. In contrast, Bayesian posterior probabilities, computed from prior knowledge and stimulus frequencies, were encoded in bilateral inferior frontal gyrus. Here activity increased for improbable events and thus signaled the violation of Bayesian predictions. Thus, subjective beliefs and stimulus frequencies were encoded in separate cortical regions. The advantage of such a separation is that objective evidence can be recombined with newly acquired knowledge when a reinterpretation of the evidence is called for. Overall this study reveals the coexistence in the brain of an experience-based system of inference and a knowledge-based system of inference

Clinical Performance of an Automated Reader in Interpreting Malaria Rapid Diagnostic Tests in Tanzania.

Parasitological confirmation of malaria is now recommended in all febrile patients by the World Health Organization (WHO) to reduce inappropriate use of anti-malarial drugs. Widespread implementation of rapid diagnostic tests (RDTs) is regarded as an effective strategy to achieve this goal. However, the quality of diagnosis provided by RDTs in remote rural dispensaries and health centres is not ideal. Feasible RDT quality control programmes in these settings are challenging. Collection of information regarding diagnostic events is also very deficient in low-resource countries. A prospective cohort of consecutive patients aged more than one year from both genders, seeking routine care for febrile episodes at dispensaries located in the Bagamoyo district of Tanzania, were enrolled into the study after signing an informed consent form. Blood samples were taken for thick blood smear (TBS) microscopic examination and malaria RDT (SD Bioline Malaria Antigen Pf/PanTM (SD RDT)). RDT results were interpreted by both visual interpretation and DekiReaderTM device. Results of visual interpretation were used for case management purposes. Microscopy was considered the "gold standard test" to assess the sensitivity and specificity of the DekiReader interpretation and to compare it to visual interpretation. In total, 1,346 febrile subjects were included in the final analysis. The SD RDT, when used in conjunction with the DekiReader and upon visual interpretation, had sensitivities of 95.3% (95% CI, 90.6-97.7) and 94.7% (95% CI, 89.8--97.3) respectively, and specificities of 94.6% (95% CI, 93.5--96.1) and 95.6% (95% CI, 94.2--96.6), respectively to gold standard. There was a high percentage of overall agreement between the two methods of interpretation. The sensitivity and specificity of the DekiReader in interpretation of SD RDTs were comparable to previous reports and showed high agreement to visual interpretation (>98%). The results of the study reflect the situation in real practice and show good performance characteristics of DekiReader on interpreting malaria RDTs in the hands of local laboratory technicians. They also suggest that a system like this could provide great benefits to the health care system. Further studies to look at ease of use by community health workers, and cost benefit of the system are warranted

Epidemiology of sexually transmitted infections among female sex workers in Switzerland: a local, exploratory, cross-sectional study

Female sex workers are often considered highly vulnerable to sexually transmitted infections (STIs). However, data on STI epidemiology in female sex workers are lacking in Switzerland. Our main goal was to evaluate the prevalence of six STIs (human immunodeficiency virus [HIV], hepatitis B, hepatitis C, Chlamydia trachomatis, Neisseria gonorrhoeae and syphilis) among local female sex workers in Lausanne. A local, exploratory, cross-sectional study was conducted on a convenience sample of adult (≥18 years) Female sex workers in Lausanne, Switzerland, from 1 April 2015 to 31 December 2016. female sex workers who worked in street sex venues, massage parlours and brothels were approached for recruitment by a local non-governmental organisation. They were then invited to present at the Lausanne University Hospital, where they were offered a free STI screening and hepatitis A and B vaccination. We enrolled 96 female sex workers. They were predominantly undocumented immigrants (60%) from Africa and Eastern Europe with no health insurance; only one participant (1%) was Swiss born. During the study, 15 (16%; 95% confidence interval [CI] 9–23%) participants were newly confirmed to have an STI: six (6%; 95% CI 1–11%) had C. trachomatis, five (5%; 95% CI 0.6-9%) latent syphilis and four (4%; 95% CI 0.1–8%) hepatitis B (three with chronic active infection and one with past exposure). No human immunodeficiency virus (HIV) infections were newly diagnosed among the participants. Nineteen (20%) of the female sex workers were already vaccinated against hepatitis B, and 73 (76%) initiated vaccination against hepatitis A and hepatitis B during the study. Forty-four (46%) of the female sex workers required translation and assistance from social services

Seismic risk in the city of Al Hoceima (north of Morocco) using the vulnerability index method, applied in Risk-UE project

The final publication is available at Springer via http://dx.doi.org/10.1007/s11069-016-2566-8Al Hoceima is one of the most seismic active regions in north of Morocco. It is demonstrated by the large seismic episodes reported in seismic catalogs and research studies. However, seismic risk is relatively high due to vulnerable buildings that are either old or don’t respect seismic standards. Our aim is to present a study about seismic risk and seismic scenarios for the city of Al Hoceima. The seismic vulnerability of the existing residential buildings was evaluated using the vulnerability index method (Risk-UE). It was chosen to be adapted and applied to the Moroccan constructions for its practicality and simple methodology. A visual inspection of 1102 buildings was carried out to assess the vulnerability factors. As for seismic hazard, it was evaluated in terms of macroseismic intensity for two scenarios (a deterministic and probabilistic scenario). The maps of seismic risk are represented by direct damage on buildings, damage to population and economic cost. According to the results, the main vulnerability index of the city is equal to 0.49 and the seismic risk is estimated as Slight (main damage grade equal to 0.9 for the deterministic scenario and 0.7 for the probabilistic scenario). However, Moderate to heavy damage is expected in areas located in the newer extensions, in both the east and west of the city. Important economic losses and damage to the population are expected in these areas as well. The maps elaborated can be a potential guide to the decision making in the field of seismic risk prevention and mitigation strategies in Al Hoceima.Peer ReviewedPostprint (author's final draft

Increased use of malaria rapid diagnostic tests improves targeting of anti-malarial treatment in rural Tanzania: implications for nationwide rollout of malaria rapid diagnostic tests.

ABSTRACT: BACKGROUND: The World Health Organization recommends parasitological confirmation of all malaria cases. Tanzania is implementing a phased rollout of malaria rapid diagnostic tests (RDTs) for routine use in all levels of care as one strategy to increase parasitological confirmation of malaria diagnosis. This study was carried out to evaluated artemisinin combination therapy (ACT) prescribing patterns in febrile patients with and without uncomplicated malaria in one pre-RDT implementation and one post-RDT implementation area. METHODS: A cross-sectional health facility surveys was conducted during high and low malaria transmission seasons in 2010 in both areas. Clinical information and a reference blood film on all patients presenting for an initial illness consultation were collected. Malaria was defined as a history of fever in the past 48 hours and microscopically confirmed parasitaemia. Routine diagnostic testing was defined as RDT or microscopy ordered by the health worker and performed at the health facility as part of the health worker-patient consultation. Correct diagnostic testing was defined as febrile patient tested with RDT or microscopy. Over-testing was defined as a febrile patient tested with RDT or microscopy. Correct treatment was defined as patient with malaria prescribed ACT. Over-treatment was defined as patient without malaria prescribed ACT. RESULTS: A total of 1,247 febrile patients (627 from pre-implementation area and 620 from post-implementation area) were included in the analysis. In the post-RDT implementation area, 80.9% (95% CI, 68.2-89.3) of patients with malaria received recommended treatment with ACT compared to 70.3% (95% CI, 54.7-82.2) of patients in the pre-RDT implementation area. Correct treatment was significantly higher in the post-implementation area during high transmission season (85.9% (95%CI, 72.0-93.6) compared to 58.3% (95%CI, 39.4-75.1) in pre-implementation area (p=0.01). Over-treatment with ACT of patients without malaria was less common in the post-RDT implementation area (20.9%; 95% CI, 14.7-28.8) compared to the pre-RDT implementation area (45.8%; 95% CI, 37.2-54.6) (p<0.01) in high transmission. The odds of overtreatment was significantly lower in post- RDT area (adjusted Odds Ratio (OR: 95%CI) 0.57(0.36-0.89); and much higher with clinical diagnosis adjusted OR (95%CI) 2.24(1.37-3.67) CONCLUSION: Implementation of RDTs increased use of RDTs for parasitological confirmation and reduced over-treatment with ACT during high malaria transmission season in one area in Tanzania. Continued monitoring of the national RDT rollout will be needed to assess whether these changes in case management practices will be replicated in other areas and sustained over time. Additional measures (such as refresher trainings, closer supervisions, etc) may be needed to improve ACT targeting during low transmission seasons

"Even if the test result is negative, they should be able to tell us what is wrong with us": a qualitative study of patient expectations of rapid diagnostic tests for malaria.

BACKGROUND: The debate on rapid diagnostic tests (RDTs) for malaria has begun to shift from whether RDTs should be used, to how and under what circumstances their use can be optimized. This has increased the need for a better understanding of the complexities surrounding the role of RDTs in appropriate treatment of fever. Studies have focused on clinician practices, but few have sought to understand patient perspectives, beyond notions of acceptability. METHODS: This qualitative study aimed to explore patient and caregiver perceptions and experiences of RDTs following a trial to assess the introduction of the tests into routine clinical care at four health facilities in one district in Ghana. Six focus group discussions and one in-depth interview were carried out with those who had received an RDT with a negative test result. RESULTS: Patients had high expectations of RDTs. They welcomed the tests as aiding clinical diagnoses and as tools that could communicate their problem better than they could, verbally. However, respondents also believed the tests could identify any cause of illness, beyond malaria. Experiences of patients suggested that RDTs were adopted into an existing system where patients are both physically and intellectually removed from diagnostic processes and where clinicians retain authority that supersedes tests and their results. In this situation, patients did not feel able to articulate a demand for test-driven diagnosis. CONCLUSIONS: Improvements in communication between the health worker and patient, particularly to explain the capabilities of the test and management of RDT negative cases, may both manage patient expectations and promote patient demand for test-driven diagnoses

133,000 Years of Sedimentary Record in a Contourite Drift in the Western Alboran Sea: Sediment Sources and Paleocurrent Reconstruction

The Djibouti Ville Drift is part of a contourite depositional system located on the southern side of the Djibouti Ville Seamount in the Alboran Sea (Western Mediterranean). The sedimentary record of a core located in the drift deposits has been characterized to achieve the possible sediment sources for the Saharan dust supply and the paleocurrent variability related to Mediterranean intermediate waters for the last 133 kyr. Three end-member grain-size distributions characterize the sediment record transported by the bottom current to address the different aeolian populations, i.e., coarse EM1, silty EM2, and fine EM3. For these particles, the most likely source areas are the Saharan sedimentary basins and deserts, as well as the cratonic basins of the Sahara-Sahel Dust Corridor. The prevalence of these main source areas is shown in the core record, where a noticeable change occurs during the MIS 5 to MIS 4 transition. Some punctual sediment inputs from the seamount have been recognized during sea-level lowstand, but there is no evidence of fluvial supply in the drift deposits. The paleocurrent reconstruction allows the characterizing of the stadial and cold periods by large increases in the mean sortable silt fraction and UP10, which point to an enhanced bottom current strength related to intermediate water masses. Conversely, interglacial periods are characterized by weaker bottom current activity, which is associated with denser deep water masses. These proxies also recorded the intensified Saharan wind transport that occurred during interstadial/stadial transitions. All these results point to the importance of combining sediment source areas with major climatic oscillations and paleocurrent variability in palaeoceanographic sedimentary archives, which may help to develop future climate prediction models.Fil: López González, Nieves. Instituto Español de Oceanografía; EspañaFil: Alonso, Belén. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Juan, Carmen. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Ercilla, Gemma. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Bozzano, Graziella. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cacho, Isabel. Universidad de Barcelona; EspañaFil: Casas, David. Instituto Geológico y Minero de España; EspañaFil: Palomino, Desirée. Instituto Español de Oceanografía; EspañaFil: Vázquez, Juan Tomás. Instituto Español de Oceanografía; EspañaFil: Estrada, Ferran. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: Bárcenas, Patricia. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias del Mar; EspañaFil: d’Acremont, Elia. Sorbonne Universités; FranciaFil: Gorini, Christian. Université Pierre et Marie Curie; Francia. Sorbonne University; FranciaFil: Moumni, Bouchta El. Université Abdelmalek Essaadi; Marrueco

Access to Artemisinin-Based Anti-Malarial Treatment and its Related Factors in Rural Tanzania.

Artemisinin-based combination treatment (ACT) has been widely adopted as one of the main malaria control strategies. However, its promise to save thousands of lives in sub-Saharan Africa depends on how effective the use of ACT is within the routine health system. The INESS platform evaluated effective coverage of ACT in several African countries. Timely access within 24 hours to an authorized ACT outlet is one of the determinants of effective coverage and was assessed for artemether-lumefantrine (Alu), in two district health systems in rural Tanzania. From October 2009 to June 2011we conducted continuous rolling household surveys in the Kilombero-Ulanga and the Rufiji Health and Demographic Surveillance Sites (HDSS). Surveys were linked to the routine HDSS update rounds. Members of randomly pre-selected households that had experienced a fever episode in the previous two weeks were eligible for a structured interview. Data on individual treatment seeking, access to treatment, timing, source of treatment and household costs per episode were collected. Data are presented on timely access from a total of 2,112 interviews in relation to demographics, seasonality, and socio economic status. In Kilombero-Ulanga, 41.8% (CI: 36.6-45.1) and in Rufiji 36.8% (33.7-40.1) of fever cases had access to an authorized ACT provider within 24 hours of fever onset. In neither of the HDSS site was age, sex, socio-economic status or seasonality of malaria found to be significantly correlated with timely access. Timely access to authorized ACT providers is below 50% despite interventions intended to improve access such as social marketing and accreditation of private dispensing outlets. To improve prompt diagnosis and treatment, access remains a major bottle neck and new more innovative interventions are needed to raise effective coverage of malaria treatment in Tanzania