National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants.

BACKGROUND: Data for trends in glycaemia and diabetes prevalence are needed to understand the effects of diet and lifestyle within populations, assess the performance of interventions, and plan health services. No consistent and comparable global analysis of trends has been done. We estimated trends and their uncertainties in mean fasting plasma glucose (FPG) and diabetes prevalence for adults aged 25 years and older in 199 countries and territories. METHODS: We obtained data from health examination surveys and epidemiological studies (370 country-years and 2·7 million participants). We converted systematically between different glycaemic metrics. For each sex, we used a Bayesian hierarchical model to estimate mean FPG and its uncertainty by age, country, and year, accounting for whether a study was nationally, subnationally, or community representative. FINDINGS: In 2008, global age-standardised mean FPG was 5·50 mmol/L (95% uncertainty interval 5·37-5·63) for men and 5·42 mmol/L (5·29-5·54) for women, having risen by 0·07 mmol/L and 0·09 mmol/L per decade, respectively. Age-standardised adult diabetes prevalence was 9·8% (8·6-11·2) in men and 9·2% (8·0-10·5) in women in 2008, up from 8·3% (6·5-10·4) and 7·5% (5·8-9·6) in 1980. The number of people with diabetes increased from 153 (127-182) million in 1980, to 347 (314-382) million in 2008. We recorded almost no change in mean FPG in east and southeast Asia and central and eastern Europe. Oceania had the largest rise, and the highest mean FPG (6·09 mmol/L, 5·73-6·49 for men; 6·08 mmol/L, 5·72-6·46 for women) and diabetes prevalence (15·5%, 11·6-20·1 for men; and 15·9%, 12·1-20·5 for women) in 2008. Mean FPG and diabetes prevalence in 2008 were also high in south Asia, Latin America and the Caribbean, and central Asia, north Africa, and the Middle East. Mean FPG in 2008 was lowest in sub-Saharan Africa, east and southeast Asia, and high-income Asia-Pacific. In high-income subregions, western Europe had the smallest rise, 0·07 mmol/L per decade for men and 0·03 mmol/L per decade for women; North America had the largest rise, 0·18 mmol/L per decade for men and 0·14 mmol/L per decade for women. INTERPRETATION: Glycaemia and diabetes are rising globally, driven both by population growth and ageing and by increasing age-specific prevalences. Effective preventive interventions are needed, and health systems should prepare to detect and manage diabetes and its sequelae. FUNDING: Bill & Melinda Gates Foundation and WHO.

Background morbidity in HIV vaccine trial participants from various geographic regions as assessed by unsolicited adverse events.

Background: Recently, more clinical trials are being conducted in Africa and Asia, therefore, background morbidity in the respective populations is of interest. Between 2000 and 2007, the International AIDS Vaccine Initiative sponsored 19 Phase 1 or 2A preventive HIV vaccine trials in the US, Europe, Sub-Saharan Africa and India, enrolling 900 healthy HIV-1 uninfected volunteers.   Objective To assess background morbidity as reflected by unsolicited adverse events (AEs), unrelated to study vaccine, reported in clinical trials from four continents. Methods All but three clinical trials were double-blind, randomized, and placebo-controlled. Study procedures and data collection methods were standardized. The frequency and severity of AEs reported during the first year of the trials were analyzed. To avoid confounding by vaccine-related events, solicited reactogenicity and other AEs occurring within 28 d after any vaccination were excluded. Results In total, 2134 AEs were reported by 76% of all participants; 73% of all events were mild. The rate of AEs did not differ between placebo and vaccine recipients. Overall, the percentage of participants with any AE was higher in Africa (83%) compared with Europe (71%), US (74%) and India (65%), while the percentage of participants with AEs of moderate or greater severity was similar in all regions except India. In all regions, the most frequently reported AEs were infectious diseases, followed by gastrointestinal disorders. Conclusions Despite some regional differences, in these healthy participants selected for low risk of HIV infection, background morbidity posed no obstacle to clinical trial conduct and interpretation. Data from controlled clinical trials of preventive interventions can offer valuable insights into the health of the eligible population.

Declining stroke and myocardial infarction mortality between 1989 and 2010 in a country of the African region.

BACKGROUND AND PURPOSE: In low- and middle-income countries, the total burden of cardiovascular diseases is expected to increase due to demographic and epidemiological transitions. However, data on cause-specific mortality are lacking in sub-Saharan Africa. Seychelles is one of the few countries in the region where all deaths are registered and medically certified. In this study, we examine trends in mortality for stroke and myocardial infarction (MI) between 1989 and 2010. METHODS: Based on vital statistics, we ascertained stroke and MI as the cause of death if appearing in any of the 4 fields for immediate, intermediate, underlying, and contributory causes in death certificates. RESULTS: Mortality rates (per 100 000, age-standardized to World Health Organization standard population) decreased from 1669/710 (men/women) in 1989 to 1991 to 1113/535 in 2008-10 for all causes, from 250/140 to 141/86 for stroke, and from 117/51 to 59/24 for MI, corresponding to proportionate decreases of 33%/25% for all-cause mortality, 44%/39% for stroke, and 50%/53% for MI over 22 years. The absolute number of stroke and MI deaths did not increase over time. In 2008 to 2010, the median age of death was 65/78 years (men/women) for all causes, 68/78 for stroke, and 66/73 for MI. CONCLUSIONS: Between 1989 and 2010, age-standardized stroke and MI mortality decreased markedly and more rapidly than all-cause mortality. The absolute number of cardiovascular disease deaths did not increase over time because the impact of population aging was fully compensated by the decline in cardiovascular disease mortality. Stroke mortality remained high, emphasizing the need to strengthen cardiovascular disease prevention and control.

Association between obesity indices and cardiovascular risk factors in late adolescence in the Seychelles.

ABSTRACT: BACKGROUND: The ability of different obesity indices to predict cardiovascular risk is still debated in youth and few data are available in sub Saharan Africa. We compared the associations between several indices of obesity and cardiovascular risk factors (CVRFs) in late adolescence in the Seychelles. METHODS: We measured body mass index (BMI), waist circumference, waist/hip ratio (WHiR), waist/height ratio (WHtR) and percent fat mass (by bioimpedance) and 6 CVRFs (blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting blood glucose and uric acid) in 423 youths aged 19-20 years from the general population. RESULTS: The prevalence of overweight/obesity and several CVRFs was high, with substantial sex differences. Except for glucose in males and LDL-cholesterol in females, all obesity indices were associated with CVRFs. BMI consistently predicted CVRFs at least as well as the other indices. Linear regression on BMI had standardized regression coefficients of 0.25-0.36 for most CVRFs (p<0.01) and ROC analysis had an AUC between 60%-75% for most CVRFs. BMI also predicted well various combinations of CVRFs: 36% of male and 16% of female lean subjects (BMI subjects (BMI >P90). CONCLUSION: There was an elevated prevalence of obesity and of several CVRFs in youths in Seychelles. BMI predicted single or combined CVRFs at least as well as other simple obesity indices.

Global alcohol exposure estimates by country, territory and region for 2005--a contribution to the Comparative Risk Assessment for the 2010 Global Burden of Disease Study.

AIMS: This study aimed to estimate the prevalence of life-time abstainers, former drinkers and current drinkers, adult per-capita consumption of alcohol and pattern of drinking scores, by country and Global Burden of Disease region for 2005, and to forecast these indicators for 2010. DESIGN: Statistical modelling based on survey data and routine statistics. SETTING AND PARTICIPANTS: A total of 241 countries and territories. MEASUREMENTS: Per-capita consumption data were obtained with the help of the World Health Organization's Global Information System on Alcohol and Health. Drinking status data were obtained from Gender, Alcohol and Culture: An International Study, the STEPwise approach to Surveillance study, the World Health Survey/Multi-Country Study and other surveys. Consumption and drinking status data were triangulated to estimate alcohol consumption across multiple categories. FINDINGS: In 2005 adult per-capita annual consumption of alcohol was 6.1 litres, with 1.7 litres stemming from unrecorded consumption; 17.1 litres of alcohol were consumed per drinker, 45.8% of all adults were life-time abstainers, 13.6% were former drinkers and 40.6% were current drinkers. Life-time abstention was most prevalent in North Africa/Middle East and South Asia. Eastern Europe and Southern sub-Saharan Africa had the most detrimental pattern of drinking scores, while drinkers in Europe (Eastern and Central) and sub-Saharan Africa (Southern and West) consumed the most alcohol. CONCLUSIONS: Just over 40% of the world's adult population consumes alcohol and the average consumption per drinker is 17.1 litres per year. However, the prevalence of abstention, level of alcohol consumption and patterns of drinking vary widely across regions of the world.

Association between weight perception and socioeconomic status among adults in the Seychelles.

BACKGROUND: Few studies have examined the association between weight perception and socioeconomic status (SES) in sub-Saharan Africa, and none made this association based on education, occupation and income simultaneously. METHODS: Based on a population-based survey (n = 1255) in the Seychelles, weight and height were measured and self-perception of one's own body weight, education, occupation, and income were assessed by a questionnaire. Individuals were considered to have appropriate weight perception when their self-perceived weight matched their actual body weight. RESULTS: The prevalence of overweight and obesity was 35% and 28%, respectively. Multivariate analysis among overweight/obese persons showed that appropriate weight perception was directly associated with actual weight, education, occupation and income, and that it was more frequent among women than among men. In a model using all three SES indicators together, only education (OR = 2.5; 95% CI: 1.3-4.8) and occupation (OR = 2.3; 95% CI: 1.2-4.5) were independently associated with appropriate perception of being overweight. The OR reached 6.9 [95% CI: 3.4-14.1] when comparing the highest vs. lowest categories of SES based on a score including all SES indicators and 6.1 [95% CI: 3.0-12.1] for a score based on education and occupation. CONCLUSIONS: Appropriately perceiving one's weight as too high was associated with different SES indicators, female sex and being actually overweight. These findings suggest means and targets for clinical and population-based interventions for weight control. Further studies should examine whether these differences in weight perception underlie differences in cognitive skills, healthy weight norms, or body size ideals.

Tuberculosis comorbidity with communicable and non-communicable diseases: integrating health services and control efforts.

Recent data for the global burden of disease reflect major demographic and lifestyle changes, leading to a rise in non-communicable diseases. Most countries with high levels of tuberculosis face a large comorbidity burden from both non-communicable and communicable diseases. Traditional disease-specific approaches typically fail to recognise common features and potential synergies in integration of care, management, and control of non-communicable and communicable diseases. In resource-limited countries, the need to tackle a broader range of overlapping comorbid diseases is growing. Tuberculosis and HIV/AIDS persist as global emergencies. The lethal interaction between tuberculosis and HIV coinfection in adults, children, and pregnant women in sub-Saharan Africa exemplifies the need for well integrated approaches to disease management and control. Furthermore, links between diabetes mellitus, smoking, alcoholism, chronic lung diseases, cancer, immunosuppressive treatment, malnutrition, and tuberculosis are well recognised. Here, we focus on interactions, synergies, and challenges of integration of tuberculosis care with management strategies for non-communicable and communicable diseases without eroding the functionality of existing national programmes for tuberculosis. The need for sustained and increased funding for these initiatives is greater than ever and requires increased political and funder commitment.

Prevalence of positive tuberculosis skin tests during 5 years of screening in a Swiss remand prison

BACKGROUND: Tuberculosis (TB) screening in prisons is recommended, but the appropriate methods remain controversial. Studies evaluating screening in remand prisons arc scarce. METHOD: Between 1997 and 2001, voluntary screening based on the tuberculin skin test (TST) was offered to all prisoners on entry into the largest remand prison in Switzerland. Prisoners with positive results underwent chest X-rays. We analysed this information collected in an anonymous database. RESULTS: A total of 4890 prisoners entered the prison and were eligible for screening; 3779 (77.3%) had TST performed on average 9 days after arrival: 46.9% were positive (induration >= 10 mm). Positive TST rates were similar over the 5 years. Women were more likely to have a negative TST (60.4%) than men (47.7%; P < 0.001, Pearson's chi(2) 16.5). Positive TSTs varied according to the prisoner's country of origin (64% for sub-Saharan Africa, 57% for Eastern Europe, 56% for North Africa, 51% for Asia and 34% for North and West Europe). CONCLUSION: The percentage of TST-positive subjects was high, and most did not receive preventive treatment for latent TB. The usefulness of systematic TST for all prisoners on entry is limited, as diagnosis of TB disease usually remains the priority in prisons. Keywords

Pre-hospital risk factors for inpatient death from severe febrile illness in malian children.

BACKGROUND: Inpatient case fatality from severe malaria remains high in much of sub-Saharan Africa. The majority of these deaths occur within 24 hours of admission, suggesting that pre-hospital management may have an impact on the risk of case fatality. METHODS: Prospective cohort study, including questionnaire about pre-hospital treatment, of all 437 patients admitted with severe febrile illness (presumed to be severe malaria) to the paediatric ward in Sikasso Regional Hospital, Mali, in a two-month period. FINDINGS: The case fatality rate was 17.4%. Coma, hypoglycaemia and respiratory distress at admission were associated with significantly higher mortality. In multiple logistic regression models and in a survival analysis to examine pre-admission risk factors for case fatality, the only consistent and significant risk factor was sex. Girls were twice as likely to die as boys (AOR 2.00, 95% CI 1.08-3.70). There was a wide variety of pre-hospital treatments used, both modern and traditional. None had a consistent impact on the risk of death across different analyses. Reported use of traditional treatments was not associated with post-admission outcome. INTERPRETATION: Aside from well-recognised markers of severity, the main risk factor for death in this study was female sex, but this study cannot determine the reason why. Differences in pre-hospital treatments were not associated with case fatality.

Visceral leishmaniasis and hemophagocytic syndrome

A 11 months old female infant from Portugal, free of family history, consults for apathy, weight loss, tachycardia, tachypnea, petechiae, pallor without icterus and hepatoslenomegaly. Seven months earlier, while being in Portugal, she presented a persistent bluish pimple on her buttock. Laboratory results showed anemia (35 g/l), leucopenia (3.3 G/l), thrombocytopenia (13 G/l), impaired coagulation (INR 1.4, PTT 41 sec.), hyponatremia (124 mmol/l), elevated CRP (139 mg/l), high ferritin (34.775 μg/l) and high triglycerides (5.22 mmol/l). After correction of vital parameters, a bone marrow aspiration and biopsy (BMB) revealed both the etiological diagnosis, namely a visceral leishmaniasis (VL) as well as one of its potential complications, the hemophagocytic syndrome (HS). Transfusions of whole blood, platelets and fresh frozen plasma were immediately started. Dexamethasone (10 mg/m2) and amphotericin B (3 mg/kg/day) have also been administrated. Visceral leishmaniasis is caused by a protozoan (Leishmania donovani) transmitted by the female sandfly. It is endemic in the Mediterranean basin (including France, Italy, Spain and Portugal), South America, sub-Saharan Africa as well as in India and Bangladesh. The parasite infects macrophages and, after several weeks of incubation, the disease occurs by affection of bloodlines (anemia, leucopenia, thrombocytopenia), hepatosplenomegaly, cachexia, gastrointestinal damage. The complications of the disease may lead to death. Liposomal amphotericin B is the currently recommended treatment. HS is caused by the proliferation and activation of macrophages in the marrow in response to a cytokine storm. It may be of primary cause. When it is secondary, it may be related to infections such as leishmaniasis. Patients present with fever and laboratory diagnostic criteria include cytopenia, hypertriglyceridemia, high ferritin and hemophagocytosis in the BMB. The treatment consists among other in the administration of high doses corticosteroids and, in secondary cases, in the treatment of the underlying cause. In conclusion, the clinical and biological features of VL may mimic haematological disorders as leukemia, but an enlargement of the liver and especially of the spleen should remind in this parasitic infection and its potential fatal complication, the HS.

Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study.

BACKGROUND: Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. METHODS: A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) co-administered with SP (AS + SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. FINDINGS: Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from <1% to 2% between the two sites and across the five survey years. A multivariable logistic regression model was fitted to adjust for age, socioeconomic status, bed net use and rainfall. In the presence of consistently high coverage and efficacy of SP monotherapy and AS + SP in the comparison and intervention areas, the introduction of ACT in the intervention site was associated with a modest reduction in the adjusted asexual parasitaemia prevalence of 5 percentage-points or 23% (p < 0.0001) relative to the comparison site. Gametocytaemia prevalence did not differ significantly (p = 0.30). INTERPRETATION: The introduction of ACT at fixed health facilities only modestly reduced asexual parasitaemia prevalence. ACT is effective for treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly re-infected.

Identification and potential origin of invasive clawed frogs Xenopus (Anura: Pipidae) in Sicily based on mitochondrial and nuclear DNA

African clawed frogs of the widespread polytypic species Xenopus laevis Daudin, 1802 (ranging large parts of sub-Saharan Africa) have been spreading since the 1940s, and have established reproductive populations in Europe, Asia and the Americas, where they can have negative impact as competitors of native amphibians and as disease vectors for chytridomycosis or ranaviruses. Here we use two mitochondrial (cytochrome b, 16S rDNA) and one nuclear (RAG 1: Recombination Associated Gene 1) DNA markers to infer the potential origin of invasive clawed frogs from Sicily that represent the largest invasive population in Europe. Identical mtDNA haplotypes match with those of Xenopus laevis, and Sicilian clawed frogs very probably belong to a lineage from the Cape Region of South Africa, most likely originating from a laboratory stock. Nuclear data support this conclusion. Identical mtDNA sequences (cyt b, 16S) of frogs sampled across their range in Sicily suggest the occurrence of a single source population and a potential bottleneck at their release, but faster evolving multilocus nuclear data (microsatellites, SNPs) on the population genetics would be important in the future to better support this hypothesis

Essential surgery: the way forward.

INTRODUCTION: Very little surgical care is performed in low- and middle-income countries (LMICs). An estimated two billion people in the world have no access to essential surgical care, and non-surgeons perform much of the surgery in remote and rural areas. Surgical care is as yet not recognized as an integral aspect of primary health care despite its self-demonstrated cost-effectiveness. We aimed to define the parameters of a public health approach to provide surgical care to areas in most need. METHODS: Consensus meetings were held, field experience was collected via targeted interviews, and a literature review on the current state of essential surgical care provision in Sub-Saharan Africa (SSA) was conducted. Comparisons were made across international recommendations for essential surgical interventions and a consensus-driven list was drawn up according to their relative simplicity, resource requirement, and capacity to provide the highest impact in terms of averted mortality or disability. RESULTS: Essential Surgery consists of basic, low-cost surgical interventions, which save lives and prevent life-long disability or life-threatening complications and may be offered in any district hospital. Fifteen essential surgical interventions were deduced from various recommendations from international surgical bodies. Training in the realm of Essential Surgery is narrow and strict enough to be possible for non-physician clinicians (NPCs). This cadre is already active in many SSA countries in providing the bulk of surgical care. CONCLUSION: A basic package of essential surgical care interventions is imperative to provide structure for scaling up training and building essential health services in remote and rural areas of LMICs. NPCs, a health cadre predominant in SSA, require training, mentoring, and monitoring. The cost of such training is vastly more efficient than the expensive training of a few polyvalent or specialist surgeons, who will not be sufficient in numbers within the next few generations. Moreover, these practitioners are used to working in the districts and are much less prone to gravitate elsewhere. The use of these NPCs performing "Essential Surgery" is a feasible route to deal with the almost total lack of primary surgical care in LMICs.

Genetic consequences of population expansions and contractions in the common hippopotamus (Hippopotamus amphibius) since the Late Pleistocene.

Over the past two decades, an increasing amount of phylogeographic work has substantially improved our understanding of African biogeography, in particular the role played by Pleistocene pluvial-drought cycles on terrestrial vertebrates. However, still little is known on the evolutionary history of semi-aquatic animals, which faced tremendous challenges imposed by unpredictable availability of water resources. In this study, we investigate the Late Pleistocene history of the common hippopotamus (Hippopotamus amphibius), using mitochondrial and nuclear DNA sequence variation and range-wide sampling. We documented a global demographic and spatial expansion approximately 0.1-0.3 Myr ago, most likely associated with an episode of massive drainage overflow. These events presumably enabled a historical continent-wide gene flow among hippopotamus populations, and hence, no clear continental-scale genetic structuring remains. Nevertheless, present-day hippopotamus populations are genetically disconnected, probably as a result of the mid-Holocene aridification and contemporary anthropogenic pressures. This unique pattern contrasts with the biogeographic paradigms established for savannah-adapted ungulate mammals and should be further investigated in other water-associated taxa. Our study has important consequences for the conservation of the hippo, an emblematic but threatened species that requires specific protection to curtail its long-term decline.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.