Spread of artemisinin resistance in Plasmodium falciparum malaria.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. METHODS: Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS: The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS: Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.).

A prospective study of the importance of enteric fever as a cause of non-malarial febrile illness in patients admitted to Chittagong Medical College Hospital, Bangladesh.

BACKGROUND: Fever is a common cause of hospital admission in Bangladesh but causative agents, other than malaria, are not routinely investigated. Enteric fever is thought to be common. METHODS: Adults and children admitted to Chittagong Medical College Hospital with a temperature of ≥38.0 °C were investigated using a blood smear for malaria, a blood culture, real-time PCR to detect Salmonella Typhi, S. Paratyphi A and other pathogens in blood and CSF and an NS1 antigen dengue ELISA. RESULTS: We enrolled 300 febrile patients with a negative malaria smear between January and June 2012: 156 children (aged ≤15 years) and 144 adults with a median (interquartile range) age of 13 (5-31) years and median (IQR) illness duration before admission of five (2-8) days. Clinical enteric fever was diagnosed in 52 patients (17.3 %), lower respiratory tract infection in 48 (16.0 %), non-specific febrile illness in 48 (16.0 %), a CNS infection in 37 patients (12.3 %), urinary sepsis in 23 patients (7.7 %), an upper respiratory tract infection in 21 patients (7.0 %), and diarrhea or dysentery in 21 patients (7.0 %). Malaria was still suspected in seven patients despite a negative microscopy test. S. Typhi was detected in blood by culture or PCR in 34 (11.3 %) of patients. Of note Rickettsia typhi and Orientia tsutsugamushi were detected by PCR in two and one patient respectively. Twenty-nine (9 %) patients died during their hospital admission (15/160 (9.4 %) of children and 14/144 (9.7 %) adults). Two of 52 (3.8 %) patients with enteric fever, 5/48 (10.4 %) patients with lower respiratory tract infections, and 12/37 (32.4 %) patients with CNS infection died. CONCLUSION: Enteric fever was confirmed in 11.3 % of patients admitted to this hospital in Bangladesh with non-malaria fever. Lower respiratory tract and CNS infections were also common. CNS infections in this location merit more detailed study due to the high mortality.

The diagnostic accuracy of three rapid diagnostic tests for typhoid fever at Chittagong Medical College Hospital, Chittagong, Bangladesh.

OBJECTIVE: To determine the diagnostic accuracy of three rapid diagnostic tests (RDTs) for typhoid fever in febrile hospitalised patients in Bangladesh. METHODS: Febrile adults and children admitted to Chittagong Medical College Hospital, Bangladesh, were investigated with Bact/Alert(®) blood cultures and real-time PCR to detect Salmonella enterica Typhi and Paratyphi A and assays for Rickettsia, leptospirosis and dengue fever. Acute serum samples were examined with the LifeAssay (LA) Test-it™ Typhoid IgM lateral flow assay detecting IgM antibodies against S. Typhi O antigen, CTKBiotech Onsite Typhoid IgG/IgM Combo Rapid-test cassette lateral flow assay detecting IgG and IgM antibodies against S. Typhi O and H antigens and SD Bioline line assay for IgG and IgM antibodies against S. Typhi proteins. RESULTS: In 300 malaria smear-negative febrile patients [median (IQR) age of 13.5 (5-31) years], 34 (11.3%) had confirmed typhoid fever: 19 positive by blood culture for S. Typhi (three blood PCR positive) and 15 blood culture negative but PCR positive for S. Typhi in blood. The respective sensitivity and specificity of the three RDTs in patients using a composite reference standard of blood culture and/or PCR-confirmed typhoid fever were 59% and 61% for LifeAssay, 59% and 74% for the CTK IgM and/or IgG, and 24% and 96% for the SD Bioline RDT IgM and/or IgG. The LifeAssay RDT had a sensitivity of 63% and a specificity of 91% when modified with a positive cut-off of ≥2+ and analysed using a Bayesian latent class model. CONCLUSIONS: These typhoid RDTs demonstrated moderate diagnostic accuracies, and better tests are needed.

Participants' perceptions and understanding of a malaria clinical trial in Bangladesh.

BACKGROUND: Existing evidence suggests that there is often limited understanding among participants in clinical trials about the informed consent process, resulting in their providing consent without really understanding the purpose of the study, specific procedures, and their rights. The objective of the study was to determine the subjects' understanding of research, perceptions of voluntariness and motivations for participation in a malaria clinical trial. METHODS: In this study semi-structured interviews of adult clinical trial participants with uncomplicated falciparum malaria were conducted in Ramu Upazila Health Complex, in Bangladesh. RESULTS: Of 16 participants, the vast majority (81%) were illiterate. All subjects had a 'therapeutic misconception' i.e. the trial was perceived to be conducted primarily for the benefit of individual patients when in fact the main objective was to provide information to inform public health policy. From the patients' perspective, getting well from their illness was their major concern. Poor actual understanding of trial specific procedures was reported despite participants' satisfaction with treatment and nursing care. CONCLUSION: There is frequently a degree of overlap between research and provision of clinical care in malaria research studies. Patients may be motivated to participate to research without a good understanding of the principal objectives of the study despite a lengthy consent process. The findings suggest that use of a standard consent form following the current ICH-GCP guidelines does not result in achieving fully informed consent and the process should be revised, simplified and adapted to individual trial settings.

A study to validate the Ten-Question-Questionnaire + for the detection of moderate to severe neurological disabilities in older Bangladeshi children.

PURPOSE: Our study validated the Ten Question Questionnaire (TQQ+) for Bangladeshi children between 10 and 16 years. The TQQ + is a rapid screening tool for disability and was previously validated in children below 9 years of age. MATERIALS AND METHODS: The study was carried out in Chattogram, Bangladesh. One hundred children aged 10-16 years, 10 with mild or moderate disabilities, 40 with severe disabilities, and 50 children without a disability were identified. Children with disability (n = 50) had previously undergone Wechsler Intelligence Scale-Revised (WISC-R) assessments by psychologists as a reference standard. Each child was evaluated using Rapid Neurodevelopmental Assessment (RNDA) by physicians and TQQ + was administered by researchers. Sensitivities and specificities of TQQ + were evaluated in comparison with RNDA and WISC-R. RESULTS: The sensitivity of TQQ + was 98% in comparison with either RNDA or WISC-R. The specificity of TQQ was 76.5% compared with RNDA and 78% with WISC-R. TQQ + successfully picked up cognitive (98%) and motor (75%) disabilities as well as behavioural problems (88.9%). Specificity was good to excellent in all other domains. Logistic regression showed that TQQ + could reliably predict disability by RNDA and WISC-R. The area under the Receiver Operating Characteristic Curve (ROC) curve was 0.88 which denoted good diagnostic accuracy of the questionnaire. CONCLUSION: The TQQ + is valid for screening disabilities in 10-16 year old Bangladeshi children.IMPLICATIONS FOR REHABILITATIONIf children with neurodevelopmental disabilities are screened early, the benefit of intervention will be greater.TQQ + is an easy to administer and low-cost tool that has been validated internationally.The TQQ + is now validated and can be used for children aged 10 to 16 years in Bangladesh.

Temporal trends in severe malaria in Chittagong, Bangladesh.

BACKGROUND: Epidemiological data on malaria in Bangladesh are sparse, particularly on severe and fatal malaria. This hampers the allocation of healthcare provision in this resource-poor setting. Over 85% of the estimated 150,000-250,000 annual malaria cases in Bangladesh occur in Chittagong Division with 80% in the Chittagong Hill Tracts (CHT). Chittagong Medical College Hospital (CMCH) is the major tertiary referral hospital for severe malaria in Chittagong Division. METHODS: Malaria screening data from 22,785 inpatients in CMCH from 1999-2011 were analysed to investigate the patterns of referral, temporal trends and geographical distribution of severe malaria in Chittagong Division, Bangladesh. RESULTS: From 1999 till 2011, 2,394 malaria cases were admitted, of which 96% harboured Plasmodium falciparum and 4% Plasmodium vivax. Infection was commonest in males (67%) between 15 and 34 years of age. Seasonality of malaria incidence was marked with a single peak in P. falciparum transmission from June to August coinciding with peak rainfall, whereas P. vivax showed an additional peak in February-March possibly representing relapse infections. Since 2007 there has been a substantial decrease in the absolute number of admitted malaria cases. Case fatality in severe malaria was 18% from 2008-2011, remaining steady during this period.A travel history obtained in 226 malaria patients revealed only 33% had been to the CHT in the preceding three weeks. Of all admitted malaria patients, only 9% lived in the CHT, and none in the more remote malaria endemic regions near the Indian border. CONCLUSIONS: The overall decline in admitted malaria cases to CMCH suggests recent control measures are successful. However, there are no reliable data on the incidence of severe malaria in the CHT, the most endemic area of Bangladesh, and most of these patients do not reach tertiary health facilities. Improvement of early treatment and simple supportive care for severe malaria in remote areas and implementation of a referral system for cases requiring additional supportive care could be important contributors to further reducing malaria-attributable disease and death in Bangladesh.

The use of placebo in a trial of rectal artesunate as initial treatment for severe malaria patients en route to referral clinics: ethical issues.

Placebo-controlled trials are controversial when individuals might be denied existing beneficial medical interventions. In the case of malaria, most patients die in rural villages without healthcare facilities. An artesunate suppository that can be given by minimally skilled persons might be of value when patients suddenly become too ill for oral treatment but are several hours from a facility that can give injectable treatment for severe disease. In such situations, by default, no treatment is (or can be) given until the patient reaches a facility, making the placebo control design clinically relevant; alternative bioequivalence designs at the facility would misrepresent reality and risk incorrect conclusions. We describe the ethical issues underpinning a placebo-controlled trial in severe malaria. To protect patients and minimise risk, all patients were referred immediately to hospital so that each had a higher chance of prompt treatment through participation. There was no difference between artesunate and placebo in patients who reached clinic rapidly; among those who could not, a single artesunate suppository significantly reduced death or permanent disability, a finding of direct and indirect benefit to patients in participating villages and elsewhere.

Altered Patterns of Compositional and Functional Disruption of the Gut Microbiota in Typhoid Fever and Nontyphoidal Febrile Illness.

BACKGROUND: Experimental murine models and human challenge studies of Salmonella Typhi infection have suggested that the gut microbiome plays an important protective role against the development of typhoid fever. Anaerobic bacterial communities have been hypothesized to mediate colonization resistance against Salmonella species by producing short-chain fatty acids, yet the composition and function of the intestinal microbiota in human patients with typhoid fever remain ill defined. METHODS: We prospectively collected fecal samples from 60 febrile patients admitted to Chittagong Medical College Hospital, Bangladesh, with typhoid fever or nontyphoidal febrile illness and from 36 healthy age-matched controls. The collected fecal samples were subjected to 16s rRNA sequencing followed by targeted metabolomics analysis. RESULTS: Patients with typhoid fever displayed compositional and functional disruption of the gut microbiota compared with patients with nontyphoidal febrile illness and healthy controls. Specifically, typhoid fever patients had lower microbiota richness and alpha diversity and a higher prevalence of potentially pathogenic bacterial taxa. In addition, a lower abundance of short-chain fatty acid-producing taxa was seen in typhoid fever patients. The differences between typhoid fever and nontyphoidal febrile illness could not be explained by a loss of colonization resistance after antibiotic treatment, as antibiotic exposure in both groups was similar. CONCLUSIONS: his first report on the composition and function of the gut microbiota in patients with typhoid fever suggests that the restoration of these intestinal commensal microorganisms could be targeted using adjunctive, preventive, or therapeutic strategies.

Can we measure cognitive constructs consistently within and across cultures? Evidence from a test battery in Bangladesh, Ghana, and Tanzania.

We developed a test battery for use among children in Bangladesh, Ghana, and Tanzania, assessing general intelligence, executive functioning, and school achievement. The instruments were drawn from previously published materials and tests. The instruments were adapted and translated in a systematic way to meet the needs of the three assessment contexts. The instruments were administered by a total of 43 trained assessors to 786 children in Bangladesh, Ghana, and Tanzania with a mean age of about 13 years (range: 7-18 years). The battery provides a psychometrically solid basis for evaluating intervention studies in multiple settings. Within-group variation was adequate in each group. The expected positive correlations between test performance and age were found and reliability indices yielded adequate values. A confirmatory factor analysis (not including the literacy and numeracy tests) showed a good fit for a model, merging the intelligence and executive tests in a single factor labeled general intelligence. Measurement weights invariance was found, supporting conceptual equivalence across the three country groups, but not supporting full score comparability across the three countries.

Safety and efficacy of short course combination regimens with AmBisome, miltefosine and paromomycin for the treatment of visceral leishmaniasis (VL) in Bangladesh.

BACKGROUND: AmBisome therapy for VL has an excellent efficacy and safety profile and has been adopted as a first-line regimen in Bangladesh. Second-line treatment options are limited and should preferably be given in short course combinations in order to prevent the development of resistant strains. Combination regimens including AmBisome, paromomycin and miltefosine have proved to be safe and effective in the treatment of VL in India. In the present study, the safety and efficacy of these same combinations were assessed in field conditions in Bangladesh. METHODS: The safety and efficacy of three combination regimens: a 5 mg/kg single dose of AmBisome + 7 subsequent days of miltefosine (2.5 mg/kg/day), a 5 mg/kg single dose of AmBisome + 10 subsequent days of paromomycin (15 mg/kg/day) and 10 days of paromomycin (15 mg/kg/day) + miltefosine (2.5 mg/kg/day), were compared with a standard regimen of AmBisome 15 mg/kg given in 5 mg/kg doses on days 1, 3 and 5. This was a phase III open label, individually randomized clinical trial. Patients from 5 to 60 years with uncomplicated primary VL were recruited from the Community Based Medical College Bangladesh (CBMC,B) and the Upazila Health Complexes of Trishal, Bhaluka and Fulbaria (all located in Mymensingh district), and randomly assigned to one of the treatments. The objective was to assess safety and definitive cure at 6 months after treatment. RESULTS: 601 patients recruited between July 2010 and September 2013 received either AmBisome monotherapy (n = 158), AmBisome + paromomycin (n = 159), AmBisome + miltefosine (n = 142) or paromomycin + miltefosine (n = 142). At 6 months post- treatment, final cure rates for the intention-to-treat population were 98.1% (95%CI 96.0-100) for AmBisome monotherapy, 99.4% (95%CI 98.2-100) for the AmBisome + paromomycin arm, 94.4% (95%CI 90.6-98.2) for the AmBisome + miltefosine arm, and 97.9% (95%CI 95.5-100) for paromomycin + miltefosine arm. There were 12 serious adverse events in the study in 11 patients that included 3 non-study drug related deaths. There were no relapses or PKDL up to 6 months follow-up. All treatments were well tolerated with no unexpected side effects. Adverse events were most frequent during treatment with miltefosine + paromomycin, three serious adverse events related to the treatment occurred in this arm, all of which resolved. CONCLUSION: None of the combinations were inferior to AmBisome in both the intention-to-treat and per-protocol populations. All the combinations demonstrated excellent overall efficacy, were well tolerated and safe, and could be deployed under field conditions in Bangladesh. The trial was conducted by the International Centre for Diarrhoeal Disease Research (ICDDR,B) and the Shaheed Suhrawardy Medical College (ShSMC), Dhaka, in collaboration with the trial sites and sponsored by the Drugs for Neglected Diseases initiative (DNDi). TRIAL REGISTRATION: ClinicalTrials.gov NCT01122771.

Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa.

Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.

An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever.

OBJECTIVES: The diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. Typhi) protein antigens and the Vi polysaccharide in a cohort of Bangladeshi febrile patients. METHODS: IgM against 12 purified antigens and the Vi polysaccharide was measured by ELISA in plasma from patients with confirmed typhoid fever (n = 32), other confirmed infections (n = 17), and healthy controls (n = 40). ELISAs with the most specific antigens were performed on plasma from 243 patients with undiagnosed febrile disease. RESULTS: IgM against the S. Typhi protein antigens correlated with each other (rho > 0.8), but not against Vi (rho < 0.6). Typhoid patients exhibited higher IgM against 11/12 protein antigens and Vi than healthy controls and those with other infections. Vi, PilL, and CdtB exhibited the greatest sensitivity and specificity. Specificity and sensitivity was improved when Vi was combined with a protein antigen, generating sensitivities and specificities of 0.80 and >0.85, respectively. Applying a dynamic cut-off to patients with undiagnosed febrile disease suggested that 34-58% had an IgM response indicative of typhoid. CONCLUSIONS: We evaluated the diagnostic potential of several S. Typhi antigens; our assays give good sensitivity and specificity, but require further assessment in differing patient populations.

The Relationship between Poverty and Healthcare Seeking among Patients Hospitalized with Acute Febrile Illnesses in Chittagong, Bangladesh.

Delays in seeking appropriate healthcare can increase the case fatality of acute febrile illnesses, and circuitous routes of care-seeking can have a catastrophic financial impact upon patients in low-income settings. To investigate the relationship between poverty and pre-hospital delays for patients with acute febrile illnesses, we recruited a cross-sectional, convenience sample of 527 acutely ill adults and children aged over 6 months, with a documented fever ≥38.0 °C and symptoms of up to 14 days' duration, presenting to a tertiary referral hospital in Chittagong, Bangladesh, over the course of one year from September 2011 to September 2012. Participants were classified according to the socioeconomic status of their households, defined by the Oxford Poverty and Human Development Initiative's multidimensional poverty index (MPI). 51% of participants were classified as multidimensionally poor (MPI>0.33). Median time from onset of any symptoms to arrival at hospital was 22 hours longer for MPI poor adults compared to non-poor adults (123 vs. 101 hours) rising to a difference of 26 hours with adjustment in a multivariate regression model (95% confidence interval 7 to 46 hours; P = 0.009). There was no difference in delays for children from poor and non-poor households (97 vs. 119 hours; P = 0.394). Case fatality was 5.9% vs. 0.8% in poor and non-poor individuals respectively (P = 0.001)-5.1% vs. 0.0% for poor and non-poor adults (P = 0.010) and 6.4% vs. 1.8% for poor and non-poor children (P = 0.083). Deaths were attributed to central nervous system infection (11), malaria (3), urinary tract infection (2), gastrointestinal infection (1) and undifferentiated sepsis (1). Both poor and non-poor households relied predominantly upon the (often informal) private sector for medical advice before reaching the referral hospital, but MPI poor participants were less likely to have consulted a qualified doctor. Poor participants were more likely to attribute delays in decision-making and travel to a lack of money (P<0.001), and more likely to face catastrophic expenditure of more than 25% of monthly household income (P<0.001). We conclude that multidimensional poverty is associated with greater pre-hospital delays and expenditure in this setting. Closer links between health and development agendas could address these consequences of poverty and streamline access to adequate healthcare.

Transorbital sonographic evaluation of normal optic nerve sheath diameter in healthy volunteers in Bangladesh.

INTRODUCTION: Measurement of optic nerve sheath diameter (ONSD) by ultrasound is increasingly used as a marker to detect raised intracranial pressure (ICP). ONSD varies with age and there is no clear consensus between studies for an upper limit of normal. Knowledge of normal ONSD in a healthy population is essential to interpret this measurement. METHODS: In a prospective observational study, ONSD was measured using a 15 MHz ultrasound probe in healthy volunteers in Chittagong, Bangladesh. The aims were to determine the normal range of ONSD in healthy Bangladeshi adults and children, compare measurements in males and females, horizontal and vertical beam orientations and left and right eyes in the same individual and to determine whether ONSD varies with head circumference independent of age. RESULTS: 136 subjects were enrolled, 12.5% of whom were age 16 or under. Median ONSD was 4.41 mm with 95% of subjects in the range 4.25-4.75 mm. ONSD was bimodally distributed. There was no relationship between ONSD and age (≥4 years), gender, head circumference, and no difference in left vs right eye or horizontal vs vertical beam. CONCLUSIONS: Ultrasonographic ONSD in Bangladeshi healthy volunteers has a narrow bimodal distribution independent of age (≥4 years), gender and head circumference. ONSD >4.75 mm in this population should be considered abnormal.

Timing of enteral feeding in cerebral malaria in resource-poor settings: a randomized trial.

BACKGROUND: Early start of enteral feeding is an established treatment strategy in intubated patients in intensive care since it reduces invasive bacterial infections and length of hospital stay. There is equipoise whether early enteral feeding is also beneficial in non-intubated patients with cerebral malaria in resource poor settings. We hypothesized that the risk of aspiration pneumonia might outweigh the potential benefits of earlier recovery and prevention of hypoglycaemia. METHOD AND FINDINGS: A randomized trial of early (day of admission) versus late (after 60 hours in adults or 36 hours in children) start of enteral feeding was undertaken in patients with cerebral malaria in Chittagong, Bangladesh from May 2008 to August 2009. The primary outcome measures were incidence of aspiration pneumonia, hypoglycaemia and coma recovery time. The trial was terminated after inclusion of 56 patients because of a high incidence of aspiration pneumonia in the early feeding group (9/27 (33%)), compared to the late feeding group (0/29 (0%)), p = 0.001). One patient in the late feeding group, and none in the early group, had hypoglycaemia during admission. There was no significant difference in overall mortality (9/27 (33%) vs 6/29 (21%), p = 0.370), but mortality was 5/9 (56%) in patients with aspiration pneumonia. CONCLUSIONS: In conclusion, early start of enteral feeding is detrimental in non-intubated patients with cerebral malaria in many resource-poor settings. Evidence gathered in resource rich settings is not necessarily transferable to resource-poor settings. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN57488577.

CMCH and MORU: a Highly Successful Collaboration.

Chittagong Medical College and Hospital (CMCH) in Chittagong, Bangladesh, and Mahidol-Oxford Tropical Medicine Research Unit (MORU) of Bangkok, Thailand, are partners in a highly successful and productive research collaboration that is now heading into its tenth year. It produced arguably one of the most important clinical trials in tropical medicine this decade, the South-East-Asia-Quinine-Artesuante-Malaria-Trial (SEAQUAMAT) study, and has continued to evolve and grow ever since. The collaboration has successfully completed a number of significant clinical studies which have given important new insights into the management and pathogenesis of malaria and, to date, generated 14 peer-reviewed international journal publications. With each passing year, the size of the collaboration continues to increase along with the number and complexity of research studies undertaken. It has also helped to provide valuable postgraduate training to develop clinical services and increase capacity for high quality research in Bangladesh. The partners have complementary knowledge, skills and expertise and share common goals and it is hoped that this will remain a highly successful collaboration long into the future.