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BackgroundArtesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria.MethodsIndividual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites.ResultsForty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P

Abstract Background Artesunate and amodiaquine (AS&AQ) is at present the world's second most widely used artemisinin-based combination therapy (ACT). It was necessary to evaluate the efficacy of ACT, recently adopted by the World Health Organization (WHO) and deployed over 80 countries, in order to make an evidence-based drug policy. Methods An individual patient data (IPD) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints. Results A total of 11,700 patients (75% under 5 years old), from 33 different sites in 16 countries were followed for 28 days. Loss to follow-up was 4.9% (575/11,700). AS&AQ was given to 5,897 patients. Of these, 82% (4,826/5,897) were included in randomized comparative trials with polymerase chain reaction (PCR) genotyping results and compared to 5,413 patients (half receiving an ACT). AS&AQ and other ACT comparators resulted in rapid clearance of fever and parasitaemia, superior to non-ACT. Using survival analysis on a modified intent-to-treat population, the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90% (the WHO cut-off) in 11/16 countries. In randomized comparative trials (n = 22), the crude efficacy of AS&AQ was 75.9% (95% CI 74.6–77.1) and the PCR-adjusted efficacy was 93.9% (95% CI 93.2–94.5). The risk (weighted by site) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT, superior to dihydroartemisinin-piperaquine (DP, in one Ugandan site), and not different from AS+SP or AL (artemether-lumefantrine). The risk of gametocyte appearance and the carriage rate of AS&AQ was only greater in one Ugandan site compared to AL and DP, and lower compared to non-ACT (p = 0.001, for all comparisons). Anaemia recovery was not different than comparator groups, except in one site in Rwanda where the patients in the DP group had a slower recovery. Conclusion AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many, but not all, the sub-Saharan African countries where it was studied. Efficacy varies between and within countries. An IPD analysis can inform general and local treatment policies. Ongoing monitoring evaluation is required.

Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance. Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/µL and age-stratified values) using estimates derived from the measured WBC value as reference. Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (× 1000 cells/µL) in age groups < 1, 1–4, 5–14 and ≥ 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/µL resulted in parasite density underestimation by a median (IQR) of 26% (4–41%) in infants < 1 year old but an overestimation by 50% (16–91%) in adults aged ≥ 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve precision of parasitaemia estimation. Imprecision of parasite clearance estimates was only affected by the within-patient WBC variability over time, and remained < 10% for 79% of patients. Conclusions: Using an assumed WBC value for parasite density estimation from a thick smear may lead to underdiagnosis of hyperparasitaemia and could adversely affect clinical management; but does not result in clinically consequential inaccuracies in the estimation of the prevalence of prolonged parasite clearance and artemisinin resistance. [ABSTRACT FROM AUTHOR]

In 2004, Cambodia, a low-income country, undertook a rapid scale-up of free antiretroviral therapy (ART) through the public sector in order to respond to the need for treatment for those living with HIV/AIDS. A cohort of patients initiating ART in a provincial national hospital was set up at the beginning of the program to monitor the impact of treatment on patients. Patients provided information on behaviors through face-to-face interviews. Medical data were obtained from clinical files. Health-related quality of life (HRQOL) was assessed using the Medical Outcomes Study 21-Items Short Form (MOS SF-21). Patients were interviewed when initiating ART and followed up at 3 months, 6 months, and each consecutive 6 months thereafter. From March 2005 through January 2008, the cohort included 549 patients followed for a total of 645 person-years. The 4.0% of patients lost to follow-up were considered dead in the analysis. Incidence of mortality was 9.1 per 100 person-years, which is comparable to international standards. HRQOL subscale scores increased dramatically in the first year after initiating ART. The mean of overall HRQOL score rose from 63.0 at baseline to 81.1 at 1 year and 89.9 at 30 months of follow-up ([chi square] for trends p < 0.001). Simultaneously, the proportion of patients with full-time employment increased from 48.8% to 95.7%.We conclude that the rapid scaling-up of ART delivery in a resource poor Asian setting dramatically improved the survival and well-being of its beneficiaries, who in turn resumed productive lives within their communities.

Improving tuberculosis case detection rate with a lay informant questionnaire: an experience from the Lao People&apos;s Democratic Republic/Amelioration du taux de detection des cas de tuberculose grace a l&apos;utilisation d&apos;un questionnaire destine aux informateurs non specialistes : experience recueillie en Republique Democratique Populaire Lao/Mejora de la deteccion de casos de tuberculosis con un cuestionario a informantes legos: experiencia ... Problem In many countries, the tuberculosis (TB) annual case detection rate is below the target of 70%. In the Lao People&apos;s Democratic Republic in 2005, it did not exceed 55%. Approach The DOTS strategy promotes passive case detection of TB. In order to increase the detection rate, we validated a questionnaire targeting lay informants at village level to notify patients with chronic cough and assessed the relevance for TB case-finding. A three-item questionnaire was sent through the district health departments to all villages in six districts in six provinces. The village headmen were asked to notify chronic cough patients. Answers were validated in a door-to-door survey (20 villages/district). In a sub-sample (four villages/district) all confirmed patients were screened for TB and paragonimiasis. Local setting Attapeu, Luang Namtha, Luang Prabang, Saravane, Savanakhet and Vientiane provinces in the Lao People&apos;s Democratic Republic. Relevant changes Lay informant questionnaires sent from district health offices to villages are cost-effective and foster interaction between the health services and remote and underserved communities. Although the correct detection of patients is highly dependent on direct respondents, a substantial number of new TB and paragonimiasis cases were consistently diagnosed in chronic cough patients. Lessons learned Out of 456 questionnaires, 295 were returned (65%). Return rates were highly variable between districts (4887%), questionnaires&apos; sensitivity (56-98%), positive predictive value (34-88%) and correlation between number of notified and confirmed patients (r. 0.26-0.78). In sub-sampled villages (13 541 population) 19 (5.1%) TB and 26 (7.0%) paragonimiasis cases were detected in 374 chronic cough patients. This quick questionnaire approach proved motivating for district authorities and village key informants, although no incentives were provided. The highly operator-dependent approach yielded a consistent detection rate of TB and paragonimiasis cases. This approach brings health services and populations in need in close contact, which is particularly crucial in remote and underserved areas. Problematique Dans de nombreux pays, le taux de detection annuel des cas de tuberculose (TB) est inferieur a la valeur visee de 70 %. En Republique democratique populaire lao, ce taux n&apos;a pas depasse 55 % pour l&apos;annee 2005. Demarche La strategie DOTS encourage la detection passive des cas de TB. En vue d&apos;accroitre le taux de detection des cas, nous avons valide un questionnaire destine a la notification par des informateurs non specialistes dans les villages des cas de toux chronique et evalue l&apos;interet de ce questionnaire pour le depistage des cas de TB. Un questionnaire en trois points a ete envoye par l&apos;intermediaire des services sanitaires de district a tous les villages de six districts de six provinces. Il etait demande aux chefs de village de notifier les cas de toux chronique. Les reponses obtenues ont ete validees par une enquete de porte a porte (20 villages/district). Dans un sous-echantillon (quatre villages/district), un depistage de la tuberculose et de la paragonimiase a ete pratique chez les cas confirmes de toux chronique. Contexte local Provinces d&apos;Attapeu, de Luang Namtha, de Luang Prabang, de Saravane, de Savanakhet et de Vientiane, en Republique democratique populaire lao. Modifications pertinentes L&apos;envoi de questionnaires destines a des informateurs non specialistes par les services sanitaires de district aux villages constitue une solution peu onereuse et favorise les contacts entre ces services et des communautes eloignees et non desservies. Bien que le depistage correct des malades depende fortement de la personne qui repond au questionnaire, la notification des cas de toux chronique a permis systematiquement de diagnostiquer un nombre supplementaire de nouveaux cas de TB et de paragonimiase. Enseignements tires Parmi les 456 questionnaires, 295 (65 %) ont ete retournes. D&apos;un district a l&apos;autre, on relevait une forte variation du taux de retour (48 a 87 %), de la sensibilite du questionnaire (56 a 98 %), de la valeur predictive positive (34 a 88 %) et du taux de correlation entre le nombre des cas notifies et celui des cas confirmes (r: 0,26 a 0,78). Dans les villages faisant partie du sous-echantillon (13 541 habitants), 19 cas de TB (5,1%) et 26 cas de paragonimiase (7,0 %) ont ete detectes chez 374 individus atteints de toux chronique. Cette demarche par questionnaire rapide s&apos;est averee motivante pour les autorites de district et les principaux informateurs des villages, malgre l&apos;absence d&apos;incitations. Bien que fortement dependante de la personne remplissant le questionnaire, elle a permis d&apos;obtenir un taux homogene de detection des cas de TB et de paragonimiase. Elle permet aussi d&apos;etablir un contact etroit entre les services sanitaires et les populations necessitant des soins, ce qui est particulierement important pour les zones reculees et non desservies. Problema En muchos paises la tasa anual de deteccion de casos de tuberculosis (TB) es inferior a la meta propuesta de170%. En la Rep0blica Democratica Popular Lao no supero el 55% en 2005. Metodo La estrategia DOTS fomenta la deteccion pasiva de casos de TB. Con el fin de aumentar la tasa de deteccion, hemos validado un cuestionario dirigido a informantes legos de los pueblos para que notifiquen los casos de tos cronica, y hemos analizado su importancia en la identificacion de casos de TB. A traves de los departamentos de salud distritales, se envio un cuestionario de tres preguntas a todos los pueblos de sels distritos de sels provincias. Se les pidio a los jefes de los pueblos que notificaran los casos de tos cronica. Las respuestas fueron validadas mediante una encuesta puerta a puerta en 20 pueblos/distrito. En una submuestra de cuatro pueblos/distrito se realizaron pruebas de deteccion de la TB y la paragonimiasis en todos Ios casos confirmados de tos cronica. Lugares estudiados Provincias de Attapeu, Luang Namtha, Luang Prabang, Saravane, Savanakhet y Vientiane de la Republica Democratica Popular Lao. Cambios pertinentes Los cuestionarios enviados por los departamentos de salud distritales a informantes legos de los pueblos son costoeficaces y fomentan la interaccion entre los servicios de salud y las comunidades remotas subatendidas. Aunque la deteccion correcta de Ios pacientes depende mucho de quienes respondan, se diagnostico un numero considerable de nuevos casos de TB y paragonimiasis en pacientes con tos cronica. Ensenanzas extraidas De los 456 cuestionarios enviados, se completaron 295 (65%). Estas cifras fueron muy variables segun Ios distritos, (48-87%), al igual que la sensibilidad (56-98%) y el valor predictivo positivo (34-88%) de los cuestionarios o la correlacion entre el numero de casos notificados y confirmados (r. 0,26-0,78). En los pueblos de la submuestra (13 541 habitantes) se detectaron 19 casos (5,1%) deTB y 26 (7,0%) de paragonimiasis entre 374 pacientes con tos cronica. Este cuestionario rapido motivo tanto a las autoridades distritales como a los informantes clave de los pueblos, pese a que no se ofrecieron incentivos. Este metodo muy dependiente del operador proporciono una tasa homogenea de deteccion de casos de TB y paragonimiasis, y pone a los servicios de salud en contacto con las poblaciones necesitadas, lo cual es especialmente importante en zonas remotas y subatendidas., Background Tuberculosis accounts for almost 2 million deaths per year worldwide. (1,2) The DOTS strategy is implemented to curb the burden of disease. The target for 2005 included 100% DOTS [...]

Background: Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia.Methods: Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7.Results: A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001).Conclusions: In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery. [ABSTRACT FROM AUTHOR]

Abstract Background The treatment gap for epilepsy is considerable in low and middle-income countries. In the Lao PDR it is estimated at over 90%. Health workers play a significant role in bridging the gap between people with epilepsy (PWE) and access to epilepsy care. In a national survey we assessed: 1) the knowledge and practices of health workers in the Lao PDR towards the disease, and, 2) patient attendance at health facilities. Methods We conducted a random three-stage sampling of health workers at the provincial, district and health center levels in 2009. Results Overall, 284 health workers were enrolled in 50 health facilities of 11 provinces: health centers 24.7%; district hospitals 23.2%; and province hospitals 52.1%. Only a minority of these (2.5%) recalled ever having received training or seeking information on epilepsy. Our survey showed a lack of knowledge in diagnosing and prescribing drugs for epilepsy, including phenobarbital, the first-line of treatment. The majority of respondents (59.9%) was unaware of the availability of antiepileptic drugs in health facilities. Only 10 (20%) health facilities, and no health centres, received people with epilepsy. It was estimated that one PWE per month receives medical attention. Traditional beliefs about PWE were common; such as the idea that epilepsy could be transmitted through saliva (63.2%). A higher attendance of PWE was observed in province hospitals where the knowledge of epilepsy care was higher. Global acceptance of people with epilepsy was low. Conclusions The low level of knowledge of epilepsy on the part of health workers may be contributing to the wide treatment gap in the Lao PDR. Improving knowledge of this disease and increasing the availability of antiepileptic drugs will reduce misconceptions about epilepsy, thus encouraging more PWE to seek treatment. Community-based educational programs and extensive advocacy for people with epilepsy only began in 2009.

To the Editor: After the 2004 outbreak of highly pathogenic avian influenza (HPAI) in poultry in Lao People's Democratic Republic (PDR), the Ministry of Health implemented extensive virologic surveillance (1,2). [...]

Abstract Background Early diagnosis and treatment (EDAT) is crucial to reducing the burden of malaria in low-income countries. In the Lao PDR, this strategy was introduced in 2004-2005 and an assessment was performed at the community level in January 2007. Methods EDAT with malaria rapid diagnostic test (MRDT) and artemisinin combination therapy (ACT) was prospectively assessed among 36 randomized village health volunteers (VHVs) and 720 patients in six malaria-endemic provinces of Laos (three pilot provinces (PP), and three non-pilots provinces (NPP)). ACT was also retrospectively assessed among 2188 patients within the same areas from June to November 2006. Two checklists were used and scores were calculated. Results EDAT performance of the VHVs was rated better in PP than in NPP (16.67% versus 38.89%, respectively, p = 0.004). Nearly all VHVs could diagnose malaria but only 16 (44%) could describe the symptoms of severe malaria. In January 2007, 31/720 (4%) patients tested positive using the Paracheck® test, 35 (5%) with microscopy (sensibility: 74.3%, specificity 99.3%, positive and negative predictive values: 83.9% and 98.7%, respectively). Patients from June to November were at higher risk of malaria: 35.19% of 2,188 febrile patients were positive (OR: 10.6, 95%CI: 7.4-15.5, p < 0.000). VHVs reported the MRDT easy to use, and yielded a satisfactory performance score. EDAT performance was rated as poor despite satisfactory results regarding ACT treatment, duration and dosages. Pre-referral treatment of severe malaria was infrequent and often inadequate, with 20% of these patients dying. Results suggest a higher mortality from severe malaria than officially reported. Shortage of ACT was frequent. Discussion and conclusion MRDT and ACT are useful and efficient and can be used by VHVs. VHVs' global EDAT performance is enhanced through training and monitoring. Persistent gaps in knowledge, care of patients and wrong treatment have to be addressed.

Abstract Background Rectal artesunate has been shown to reduce death and disability from severe malaria caused by delays in reaching facilities capable of providing appropriate treatment. Acceptability of this mode of drug delivery in Laos is not known. In 2009 the acceptability of rectal treatments was evaluated among the general Lao population and Lao doctors in a national survey. Methods A cross sectional survey was performed of 985 households selected through a multi-stage random sampling process from 85 villages in 12/18 provinces and of 315 health staff randomly selected at each administrative level. Results Out of 985 families, 9% had used the rectal route to treat children (the main indication was seizures or constipation). The population considered it less effective than other routes. Other concerns raised included pain (28%), discomfort for children (40%) and the possibility of other side effects (20%). Of 300 health staff surveyed (nurses 44%, doctors 66%), only 51% had already used the rectal route with a suppository, mostly to treat fever (76%). Health staff working in provincial hospitals had more experience of using the rectal route than those in urban areas. The majority (92%) were keen to use the rectal route to treat malaria although oral and intramuscular routes were preferred and considered to be more efficacious. Discussion and conclusion Use of rectal treatments is uncommon in Laos and generally not considered to be very effective. This view is shared by the population and health care workers. More information and training are needed to convince the population and health staff of the efficacy and advantages of the rectal route for malaria treatment.

Abstract Background In Laos, small backyard poultry systems predominate (90%). The first lethal human cases of highly pathogenic avian influenza (HPAI) occurred in 2007. Few studies have addressed the impact of outbreaks and education campaigns on a smallholder producer system. We evaluated awareness and behaviours related to educational campaigns and the 2007 HPAI outbreaks. Methods During a national 2-stage cross-sectional randomised survey we interviewed 1098 households using a pre-tested questionnaire in five provinces representative of the Southern to Northern strata of Laos. We used multivariate analysis (Stata, version 8; Stata Corporation, College Station, TX, USA) to analyse factors affecting recollection of HPAI educational messages, awareness of HPAI, and behaviour change. Results Of the 1098 participants, 303 (27.6%) received training on HPAI. The level of awareness was similar to that in 2006. The urban population considered risk to be decreased, yet unsafe behaviours persisted or increased. This contrasted with an increase in awareness and safe behaviour practices in rural areas. Reported behaviour changes in rural areas included higher rates of cessation of poultry consumption and dead poultry burial when compared to 2006. No participants reported poultry deaths to the authorities. Overall, 70% could recall an educational message but the content and accuracy differed widely depending on training exposure. Washing hands and other hygiene advice, messages given during the HPAI educational campaign, were not recalled. Trained persons were able to recall only one message while untrained participants recalled a broader range of messages. Factors associated with an awareness of a threat of AI in Laos were: having received HPAI training, literacy level, access to TV, recent information, living in rural areas. Conclusion We report a paradoxical relationship between unsafe behaviours and risk perception in urban areas, as well as exposure to HPAI training and message misinterpretation. Future educational campaigns need to be tailored to specific target populations and farming styles, for example, small holder farms as compared to commercial farms. Special attention must be given to varying risk perceptions and the risk of misinterpretation of key messages, economic hardship, and real life consequences of reporting.

Abstract Background Contact tracing of tuberculosis (TB) patients is rarely performed in low-income countries. Our objective was to assess the outcome of and compliance with directly observed treatment (DOTS) of TB patients over a 3 year period in rural Lao PDR. Methods We performed a retrospective cohort study in which we enrolled TB patients who started DOTS treatment at Attapeu Provincial Hospital. We traced, through hospital records, all patients in their residential village. We conducted a standardized questionnaire with all TB patients and performed physical and anthropometric examinations as well as evaluations of compliance through counting of treatment pills at home and at the health facilities. Results Of 172 enrolled TB patients (sex ratio female/male: 0.52, mean age: 46.9 years ± 16.9), 26 (15.1%) died. These had a lower weight at the start (34.6 vs. 40.8 kg, p < 0.001) and were less compliant (91.6% vs. 19.2%, p < 0.001) than survivors. Low compliance was associated with poor accessibility to health care (p = 0.01) and symptomatic improvement (p = 0.02). Survivors had persistently poor health status. They were underweight (54.7%), and still had clinical symptoms (53.5%), including dyspnoea (28.8%) and haemoptysis (9.5%). Conclusion Our study suggests a lower rate of survival than expected from official statistics. Additionally, it showed that follow-up of TB patients is feasible although the patients lived in very remote area of Laos. Follow-up should be strengthened as it can improve patient compliance, and allow contact tracing, detection of new cases and collection of accurate treatment outcome information.

Abstract Background Artesunate and amodiaquine (AS&AQ) is at present the world's second most widely used artemisinin-based combination therapy (ACT). It was necessary to evaluate the efficacy of ACT, recently adopted by the World Health Organization (WHO) and deployed over 80 countries, in order to make an evidence-based drug policy. Methods An individual patient data (IPD) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints. Results A total of 11,700 patients (75% under 5 years old), from 33 different sites in 16 countries were followed for 28 days. Loss to follow-up was 4.9% (575/11,700). AS&AQ was given to 5,897 patients. Of these, 82% (4,826/5,897) were included in randomized comparative trials with polymerase chain reaction (PCR) genotyping results and compared to 5,413 patients (half receiving an ACT). AS&AQ and other ACT comparators resulted in rapid clearance of fever and parasitaemia, superior to non-ACT. Using survival analysis on a modified intent-to-treat population, the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90% (the WHO cut-off) in 11/16 countries. In randomized comparative trials (n = 22), the crude efficacy of AS&AQ was 75.9% (95% CI 74.6–77.1) and the PCR-adjusted efficacy was 93.9% (95% CI 93.2–94.5). The risk (weighted by site) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT, superior to dihydroartemisinin-piperaquine (DP, in one Ugandan site), and not different from AS+SP or AL (artemether-lumefantrine). The risk of gametocyte appearance and the carriage rate of AS&AQ was only greater in one Ugandan site compared to AL and DP, and lower compared to non-ACT (p = 0.001, for all comparisons). Anaemia recovery was not different than comparator groups, except in one site in Rwanda where the patients in the DP group had a slower recovery. Conclusion AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many, but not all, the sub-Saharan African countries where it was studied. Efficacy varies between and within countries. An IPD analysis can inform general and local treatment policies. Ongoing monitoring evaluation is required.

Abstract Background Tuberculosis is highly prevalent in Laos (289 per 100,000). We evaluated the risk of latent tuberculosis infection (LTBI) among children (0–15 years) living with tuberculosis patients in rural northern Laos. Methods In a cross sectional survey of 30 randomly selected villages, 72 tuberculosis patients were traced and their 317 contacts (148 were children) investigated using a questionnaire, a tuberculin skin tests (positive: > = 10 mm), a 3-day sputum examination for acid-fast bacilli (AFB), and chest radiography. Results None of the 148 contact-children received prophylaxis, one had cervical tuberculosis; the risk for LTBI was 31.0%. Awareness of the infectiousness of tuberculosis was low among patients (31%) and their contacts (31%), and risky behavior was common. After multivariate logistic analysis, increased LTBI was found in children with contact with sputum positive adults (OR: 3.3, 95% CI: 1.4–7.7), patients highly positive sputum prior to treatment (AFB >2+; OR: 4.7, 95% CI: 1.7–12.3), and living in ethnic minorities (OR: 5.4, 95% CI: 2.2–13.6). Conclusion The study supports the importance of contact tracing in remote settings with high TB prevalence. Suggestions to improve the children's detection rate, the use of existing guidelines, chemoprophylaxis of contact-children and the available interventions in Laos are discussed. Improving education and awareness of the infectiousness of TB in patients is urgently needed to reduce TB transmission.

Abstract Background Hypoglycaemia is a poor prognostic indicator in severe malaria. Intravenous infusions are rarely feasible in rural areas. The efficacy of sublingual sugar (SLS) was assessed in a pilot randomized controlled trial among hypoglycaemic children with severe malaria in Mali. Methods Of 151 patients with presumed severe malaria, 23 children with blood glucose concentrations < 60 mg/dl (< 3.3 mmol/l) were assigned randomly to receive either intravenous 10% glucose (IVG; n = 9) or sublingual sugar (SLS; n = 14). In SLS, a teaspoon of sugar, moistened with a few drops of water, was gently placed under the tongue every 20 minutes. The child was put in the recovery position. Blood glucose concentration (BGC) was measured every 5–10 minutes for the first hour. All children were treated for malaria with intramuscular artemether. The primary outcome measure was treatment response, defined as reaching a BGC of >= 3.3 mmol/l (60 mg/dl) within 40 minutes after admission. Secondary outcome measures were early treatment response at 20 minutes, relapse (early and late), maximal BGC gain (CGmax), and treatment delay. Results There was no significant difference between the groups in the primary outcome measure. Treatment response occurred in 71% and 67% for SLS and IVG, respectively. Among the responders, relapses occurred in 30% on SLS at 40 minutes and in 17% on IVG at 20 minutes. There was one fatality in each group. Treatment failures in the SLS group were related to children with clenched teeth or swallowing the sugar, whereas in the IVG group, they were due to unavoidable delays in beginning an infusion (median time 17.5 min (range 3–40). Among SLS, the BGC increase was rapid among the nine patients who really kept the sugar sublingually. All but one increased their BGC by 10 minutes with a mean gain of 44 mg/dl (95%CI: 20.5–63.4). Conclusion Sublingual sugar appears to be a child-friendly, well-tolerated and effective promising method of raising blood glucose in severely ill children. More frequent repeated doses are needed to prevent relapse. Children should be monitored for early swallowing which leads to delayed absorption, and in this case another dose of sugar should be given. Sublingual sugar could be proposed as an immediate "first aid" measure while awaiting intravenous glucose. In many cases it may avert the need for intravenous glucose.