Spirulina as a daily nutritional supplement of young pre-school Cambodian children of deprived settings: a single-blinded, placebo-controlled, cross-over trial.

BACKGROUND: Spirulina (SP) is widely used as a nutritional supplement to enhance child nutrition in low-income countries. We assessed Spirulina's efficacy of the current dose supplied by institutions in Cambodia on improving growth and anemia in a cross-over randomized controlled trial in preschool underprivileged children from similar settings. METHODS: Preschool children cared by a not-for-profit institution were randomly and blindly allocated (2 to 1) to spirulina or placebo: 100 g in total, given in 2 g per day. After 5 weeks of wash-out, participants were crossed-over to the other group. Anthropometric gain and selected hematological data (blood cell count, ferritin, and C-reactive protein) were assessed at each phase. RESULTS: A total of 179 children completed the trial, 149 (83.2%) completed all the anthropometrics, and 99 (55.3%) all hematological measures. Mean BMI was 14.18 (95%CI: 14.00-14.37) and 31(20.8%) children had thinness. Mean blood hemoglobin was 11.9 g/dL (95%CI: 11.8-12.1). The weight gain of the SP group showed a modest higher trend compared to placebo (0.63 kg; 95%CI: 0.54-0.72 and 0.46 kg; 95%CI: 0.33-0.58, respectively; p = 0.07). Height increased similarly in both groups. The number of anemic children decreased by 6 (6.06%) and 11 (11.11%) on Placebo or SP, respectively (p = 0.004). Tolerance was good. CONCLUSION: SP may be recommended to improve childhood anemia. The analysis of the usual daily dose (2 g) provided by organizations in Cambodia shows a tendency to improve weight gain in the group supplemented with SP very close to significance, but no trend in height. Increased doses and longer supplementation should be evaluated further. TRIAL REGISTRATION: The study was retrospectively registered at ISRCTN under number 11696165 on 12/12/2018.

Seroprevalence and risk factors of hepatitis E among women of childbearing age in the Xieng Khouang province (Lao People's Democratic Republic), a cross-sectional survey.

BACKGROUND: Endemic hepatitis E in Southeast Asia increases the risk of death in pregnant women. In Lao People's Democratic Republic, infection with hepatitis E virus (HEV) is widespread in pig farms. No human data are available yet. This study determined the prevalence and risk factors for HEV infection among women of reproductive age living in urban and rural areas. METHODS: A cross-sectional study was conducted in Xieng Khouang province, selected for its high prevalence of HEV in pig farms, after a two-stage random sampling. Blood eluates of filter paper samples were tested by enzyme-linked immunosorbent assay for anti-HEV immunoglobulin G (IgG). Risk factors were investigated by bivariate and multivariate analyses. RESULTS: Of 226 women (112 rural and 114 urban), anti-HEV IgG was detected in 66 (29.2%), with more in rural than in urban areas (38.4% vs 20.2%; p=0.005). Age (25-29 y) and farming profession were associated with HEV positivity. Living in an urban area, a supply of clean drinking water and raw duck blood consumption were protective. CONCLUSIONS: Risks of HEV infection are more related to lack of drinking water resources than to promiscuity with pigs. Women of childbearing age could be targeted by future vaccination programs. Consumption of drinking water should be recommended during pregnancy.

Hepatitis E virus antibody prevalence, RNA frequency, and genotype among blood donors in Cambodia (Southeast Asia).

BACKGROUND: Recent studies conducted in developed countries described hepatitis E virus (HEV) as an emerging infectious threat to blood safety. However, data on HEV among blood donors from southeast Asia are lacking. STUDY DESIGN AND METHODS: Between July and August 2014, we assessed the presence of HEV immunoglobulin (Ig)G and IgM in 301 Cambodian blood donors. All samples were further tested for the presence of HEV RNA using an in-house reverse transcription-polymerase chain reaction. ORF2/ORF3 phylogenetic analysis was performed on positive HEV RNA specimens. RESULTS: We found HEV IgG in 28.2% of blood donors from Cambodia. Three blood donors tested positive for HEV IgM with three distinct patterns: IgM(+)/IgG(-)/RNA(-) (n = 1), IgM(+)/IgG(+)/RNA(-) (n = 1), and IgM(+)/IgG(+)/RNA(+) (n = 1). Thus, the prevalence rates of HEV IgM and HEV RNA were 1.0 and 0.3%. Interestingly, the viremic blood donor harbored a HEV strain that belonged to Genotype 3 (HEV-3) and clustered with a Cambodian riverine HEV-3 isolate. CONCLUSION: Due to the high frequency of Cambodian blood donors with positive HEV IgG, we conclude that HEV is endemic in this country. Large-scale studies must be considered to determine whether Cambodian blood donation screening is warranted to enhance blood safety in regard to HEV. In addition, our findings suggest that river water may be a significant source of exposure to HEV-3.

High Mortality Risk in Hypoglycemic and Dysglycemic Children Admitted at a Referral Hospital in a Non Malaria Tropical Setting of a Low Income Country.

INTRODUCTION: Hypoglycemia is a recognized feature of severe malaria but its diagnosis and management remain problematic in resource-limited settings. There is limited data on the burden and prognosis associated with glycemia dysregulation in non-neonate children in non-malaria areas. We prospectively assessed the abnormal blood glucose prevalence and the outcome and risk factors of deaths in critically ill children admitted to a national referral hospital in Laos. METHODS: Consecutive children (1 month-15 years) admitted to the pediatric ward of Mahosot hospital, were categorized using the integrated management of childhood illness (IMCI). Blood glucose was assessed once on admission through a finger prick using a bedside glucometer. Glycemia levels: hypoglycemia: < 2.2 mmol/L (< 40 mg/ dl), low glycemia: 2.2-4.4 mmol/L (40-79 mg/ dl), euglycemia: 4.4-8.3 mmol/L (80-149 mg/ dl), and hyperglycemia: > 8.3 mmol/L (≥150 mg/ dl), were related to the IMCI algorithm and case fatality using univariate and multivariate analysis. RESULTS: Of 350 children, 62.2% (n = 218) were severely ill and 49.1% (n = 172) had at least one IMCI danger sign. A total of 15 (4.2%, 95%CI: 2.4-6.9) had hypoglycemia, 99 (28.2%, 95%CI: 23.6-33.3) low glycemia, 201 (57.4%, 95% CI: 52.0-62.6) euglycemia and 35 (10.0%, 95% CI: 7.0-13.6) hyperglycemia. Hypoglycemia was associated with longer fasting (p = 0.001) and limited treatment before admission (p = 0.09). Hypoglycemia and hyperglycemia were associated with hypoxemia (SaO2) (p = 0.001). A total of 21 (6.0%) of the children died: 66.6% with hypoglycemic, 6.0% with low glycemic, 5.7% with hyperglycemic and 1.4% with euglycemic groups. A total of 9 (2.5%) deaths occurred during the first 24 hours of admission and 5 (1.7%) within 3 days of hospital discharge. Compared to euglycemic children, hypoglycemic and low glycemic children had a higher rate of early death (20%, p<0.001 and 5%, p = 0.008; respectively). They also had a higher risk of death (OR: 132; 95%CI: 29.0-596.5; p = 0.001; and OR: 4.2; 95%CI: 1.1-15.6; p = 0.02; respectively). In multivariate analyses, hypoglycemia (OR: 197; 95%CI: 33-1173.9), hypoxemia (OR: 5.3; 95%CI: 1.4-20), presence of hepatomegaly (OR: 8.7; 95%CI: 2.0-37.6) and having an illiterate mother (OR: 25.9; 95%CI: 4.2-160.6) were associated with increased risk of death. CONCLUSION: Hypoglycemia is linked with a high risk of mortality for children in non malaria tropical settings. Blood sugar should be monitored and treatment provided for sick children, especially with danger signs and prolonged fasting. Further evaluations of intervention using thresholds including low glycemia is recommended in resource-limited settings. Research is also needed to determine the significance, prognosis and care of hyperglycemia.

Factors associated with the failure of first and second-line antiretroviral therapies therapy, a case control study in Cambodian HIV-1 infected children.

BACKGROUND: Little is known about the efficacy of first and and second-line antiretroviral therapies (ART) for HIV-1 infected children in resource limited Southeast Asian settings. Previous studies have shown that orphans are at a higher risk for virological failure (VF) in Cambodia. Consequently most of them required transfer to second-line ART. We assessed the factors associated with VF among HIV-1 infected children who were either under first-line (mostly 3TC + D4T + NVP) or under second-line (mostly ABC + DDI + LPV) therapies at a referral hospital in Cambodia. METHODS: A case-control study was conducted from February to July 2013 at the National Pediatric Hospital among HIV-1 infected children (aged 1-15 years) under second-line ART (cases) or first-line (matched controls at a ratio of 1:3) regimens. Children were included if a HIV-1 RNA plasma viral load (VL) result was available for the preceding 12 months. A standardized questionnaire explored family sociodemographics, HIV history, and adherence to ART. Associations between VF (HIV-1 RNA levels ≥1000 copies/ml) and the children's characteristics were assessed using bivariate and multivariate analyses. RESULTS: A total of 232 children, 175 (75.4 %) under first-line and 57 (24.6 %) under second-line ART, for a median of 72.0 (IQR: 68.0-76.0) months, were enrolled. Of them, 94 (40.5 %) were double orphans and 51 (22.0 %) single orphans, and 77 (33.2 %) were living in orphanages. A total of 222 children (95.6 %) were deemed adherent to ART. Overall, 18 (7.7 %; 95 % CI 4.6-11.9) showed a VF, 14 (8.6 %; 95 % CI 4.8-14.0) under first-line and 4 (7.0 %; 95 % CI 1.9-17.0) under second-line ART (p = 0.5). Their median CD4 percentage was 8 % (IQR 2.9-12.9) at ART initiation. Children under second-line ART were older; more often double orphans, and had lower CD4 cell counts at the last control. In the multivariate analysis, having the last CD4 percentage below 15 % was the only factor associated with VF for ART regimen separately or when combined (OR 40.4; 95 % CI 11-134). CONCLUSIONS: The pattern of risk factors for VF in children is changing in Cambodia. Improved adherence evaluation and intensified monitoring of children with low CD4 counts is needed to decrease the risk of VF.

Caring for patients with rabies in developing countries - the neglected importance of palliative care.

Although limited publications address clinical management of symptomatic patients with rabies in intensive care units, the overwhelming majority of human rabies cases occur in the rural setting of developing countries where healthcare workers are few, lack training and drugs. Based on our experience, we suggest how clinicians in resource-limited settings can make best use of essential drugs to provide assistance to patients with rabies and their families, at no risk to themselves. Comprehensive and compassionate patient management of furious rabies should aim to alleviate thirst, anxiety and epileptic fits using infusions, diazepam or midazolam and antipyretic drugs via intravenous or intrarectal routes. Although the patient is dying, respiratory failure must be avoided especially if the family, after being informed, wish to take the patient home alive for funereal rites to be observed. Healthcare staff should be trained and clinical guidelines should be updated to include palliative care for rabies in endemic countries.

Enforcing the International Code of Marketing of Breast-milk Substitutes for Better Promotion of Exclusive Breastfeeding: Can Lessons Be Learned?

Exclusive breastfeeding, one of the best natural resources, needs protection and promotion. The International Code of Marketing of Breast-milk Substitutes (the Code), which aims to prevent the undermining of breastfeeding by formula advertising, faces implementation challenges. We reviewed frequently overlooked challenges and obstacles that the Code is facing worldwide, but particularly in Southeast Asia. Drawing lessons from various countries where we work, and following the example of successful public health interventions, we discussed legislation, enforcement, and experiences that are needed to successfully implement the Code. Successful holistic approaches that have strengthened the Code need to be scaled up. Community-based actions and peer-to-peer promotions have proved successful. Legislation without stringent enforcement and sufficient penalties is ineffective. The public needs education about the benefits and ways and means to support breastfeeding. It is crucial to combine strong political commitment and leadership with strict national regulations, definitions, and enforcement. National breastfeeding committees, with the authority to improve regulations, investigate violations, and enforce the laws, must be established. Systematic monitoring and reporting are needed to identify companies, individuals, intermediaries, and practices that infringe on the Code. Penalizing violators is crucial. Managers of multinational companies must be held accountable for international violations, and international legislative enforcement needs to be established. Further measures should include improved regulations to protect the breastfeeding mother: large-scale education campaigns; strong penalties for Code violators; exclusion of the formula industry from nutrition, education, and policy roles; supportive legal networks; and independent research of interventions supporting breastfeeding.

Low frequency of acute hepatitis E virus (HEV) infections but high past HEV exposure in subjects from Cambodia with mild liver enzyme elevations, unexplained fever or immunodeficiency due to HIV-1 infection.

BACKGROUND: In Cambodia, previous studies conducted on hepatitis E virus (HEV) infection are scant, sometimes old, and showed inconsistent results. Moreover, there is no data about HEV infection in Cambodian HIV-1-infected patients. OBJECTIVES: To assess the occurrence of acute HEV infections and the level of past HEV exposure in one Mekong country. STUDY DESIGN: Using anti-HEV IgM and HEV RNA detection, we retrospectively investigated the presence of acute HEV infection in 825 individuals, including 350 subjects with or without fever, 300 subjects with or without liver enzyme elevations (LEE) and 175 antiretroviral treatment (ART)-naïve, severely immunocompromised HIV-1-infected patients. The detection of anti-HEV IgG was also performed to assess ancient HEV exposure. RESULTS: Nine individuals tested positive for anti-HEV IgM yielding an overall rate of 1.1% (95% confidence interval (CI), 0.5-2.0). We did not find significant differences for anti-HEV IgM rates between subjects with unexplained fevers (1.5%) and those with malaria or dengue-associated fever (1.7%) or non-febrile individuals (0%) (P=0.49), and between subjects with (1.5%) and without (2.0%) LEE (P=0.87). No HIV-infected patient tested positive for anti-HEV IgM. HEV RNA was not detected in all tested plasma specimens (n=578). Overall, the anti-HEV IgG prevalence rate was 30.1% (95% CI, 27.0-33.2). CONCLUSIONS: The scarcity of recent HEV infection contrasted with the high level of past HEV exposure. The role of HEV in liver disease is likely minor in Cambodia since no HEV RNA was detected in our studied populations, including HIV-positive patients with severe immunodepression.

Evidence of High Out of Pocket Spending for HIV Care Leading to Catastrophic Expenditure for Affected Patients in Lao People's Democratic Republic.

BACKGROUND: The scaling up of antiviral treatment (ART) coverage in the past decade has increased access to care for numerous people living with HIV/AIDS (PLWHA) in low-resource settings. Out-of-pocket payments (OOPs) represent a barrier for healthcare access, adherence and ART effectiveness, and can be economically catastrophic for PLWHA and their family. We evaluated OOPs of PLWHA attending outpatient and inpatient care units and estimated the financial burden for their households in the Lao People's Democratic Republic. We assumed that such OOPs may result in catastrophic health expenses in this context with fragile economical balance and low health insurance coverage. METHODS: We conducted a cross-sectional survey of a randomized sample of routine outpatients and a prospective survey of consecutive new inpatients at two referral hospitals (Setthathirat in the capital city, Savannaket in the province). After obtaining informed consent, PLWHA were interviewed using a standardized 82-item questionnaire including information on socio-economic characteristics, disease history and coping strategies. All OOPs occurring during a routine visit or a hospital stay were recorded. Household capacity-to-pay (overall income minus essential expenses), direct and indirect OOPs, OOPs per outpatient visit and per inpatient stay as well as catastrophic spending (greater than or equal to 40% of the capacity-to-pay) were calculated. A multivariate analysis of factors associated with catastrophic spending was conducted. RESULTS: A total of 320 PLWHA [280 inpatients and 40 outpatients; 132 (41.2%) defined as poor, and 269 (84.1%) on ART] were enrolled. Monthly median household income, essential expenses and capacity-to-pay were US$147.0 (IQR: 86-242), $126 (IQR: 82-192) and $14 (IQR: 19-80), respectively. At the provincial hospital OOPs were higher during routine visits, but three fold lower during hospitalization than in the central hospital ($21.0 versus $18.5 and $110.8 versus $329.8 respectively (p<0.01). The most notable OOPs were related to transportation and to loss of income. A total of 150 patients (46.8%; 95%CI: 41.3-52.5) were affected by catastrophic health expenses; 36 outpatients (90.0%; 95%CI: 76.3-97.2) and 114 inpatients (40.7%; 95%CI: 34.9-46.7). A total of 141 (44.0%) patients had contracted loans, and 127 (39.6%) had to sell some of their assets. In the multivariate analysis, being of Lao Loum ethnic group (Coef.-1.4; p = 0.04); being poor (Coef. -1.0; p = 0.01) and living more than 100 km away from the hospital (Coef.-1.0; p = 0.002) were positively associated with catastrophic spending. Conversely being in the highest wealth quartile (Coef. 1.6; p<0.001), living alone (Coef. 1.1; p = 0.04), attending the provincial hospital (Coef. 1.0; p = 0.002), and being on ART (Coef.1.2; p = 0.003), were negatively associated with catastrophic spending. CONCLUSION: PLWHA's households face catastrophic OOPs that are not directly attributable to the cost of ART or to follow-up tests, particularly during a hospitalization period. Transportation, distance to healthcare and time spent at the health facility are the major contributors for OOPs and for indirect opportunity costs. Being on ART and attending the provincial hospital were associated with a lower risk of catastrophic spending. Decentralization of care, access to ART and alleviation of OOPs are crucial factors to successfully decrease the household burden of HIV-AIDS expenses.

An organizational analysis of road traffic crash prevention to explain the difficulties of a national program in a low income country.

BACKGROUND: Road traffic crashes (RTC), that daily kill 3400 people and leave 15,000 with a permanent disability could be prevented through the implementation of safety programs developed in partnership with governments and institutions. The relationship between key stakeholders can be a crucial determinant to the effectiveness of road safety programs. This issue has rarely been addressed. We conducted a detailed organizational analysis of the stakeholders involved in road safety programs in Lao People's Democratic Republic (Lao PDR). METHODS: A case study was performed. The framework used was a snowball effect in which the characterization of all key stakeholders and the links between them, as well as the factors that led to these links, were determined. The effect of the relations between key stakeholders on the prevention of RTC was assessed through an analysis of the transactional, intangible and controlling factors that influence these relationships. RESULTS: The design and implementation of road safety programs in Lao PDR suffer from weak relationships between stakeholders and a poorly functional bicephal leadership between the Ministry of Public Works and Transport and the non-governmental organisation called Handicap International. This poor coordination between key stakeholders is evident, particularly in the area of collective action and is reinforced by a lack of interest from several different stakeholders. Most agencies do not prioritize road safety. Uneven distribution of funding is another contributing factor. Strengthening the leadership is crucial to the success of the program. Some organisations have skills, power the decision making and the allocation of resources in regards to road safety programs. Encouraging participation of these organizations through a more prominent position would thus result in a better collaboration. Non-monetary rewards would further help to strengthen collaborative work. CONCLUSION: The bicephal nature of the leadership of road safety programs proves detrimental, is associated with a weak coalition between stakeholders, and contributes to the declaimed poor effectiveness of the existing programs. The study has identified non-monetary and realistic means of strengthening the collaboration between key stakeholders. Stakeholders need to revise their interpretive schemes, in order to actively support the reinforcement of government leadership of road safety policies.

Reasons for routine episiotomy: A mixed-methods study in a large maternity hospital in Phnom Penh, Cambodia.

First documented in 1741, the practice of episiotomy substantially increased worldwide during the 20th century. However, research shows that episiotomy is not effective in reducing severe perineal trauma and may be harmful. Using a mixed-methods approach, we conducted a study in 2013-14 on why obstetricians and midwives in a large maternity hospital in Phnom Penh, Cambodia, still do routine episiotomies. The study included the extent of the practice, based on medical records; a retrospective analysis of the delivery notes of a random sample of 365 patients; and 22 in-depth interviews with obstetricians, midwives and recently delivered women. Of the 365 women, 345 (94.5%, 95% CI: 91.7-96.6) had had an episiotomy. Univariate analysis showed that nulliparous women underwent episiotomy more frequently than multiparous women (OR 7.1, 95% CI 2.0-24.7). The reasons given for this practice by midwives and obstetricians were: fear of perineal tears, the strong belief that Asian women have a shorter and harder perineum than others, lack of time in overcrowded delivery rooms, and the belief that Cambodian women would be able to have a tighter and prettier vagina through this practice. A restrictive episiotomy policy and information for pregnant women about birthing practices through antenatal classes should be implemented as soon as possible.

Insect Consumption to Address Undernutrition, a National Survey on the Prevalence of Insect Consumption among Adults and Vendors in Laos.

BACKGROUND: Insect consumption (entomophagy) is a potentially high nutritious and healthy source of food with high fat, protein, vitamin, fiber and micronutrient content. At least 2 billion people globally eat insects (over 1900 edible species) though this habit is regarded negatively by others. There is a limited amount of data on the perception and consumption of insects. We conducted a national cross-sectional survey in the Lao People's Democratic Republic (Laos) to assess the prevalence and characteristics of insect consumption among adult lay people and insect vendors. METHODS: We conducted a multi stage randomized national survey in 1303 households in 96 villages in 16 Lao provinces. Three insect vendors or collectors per village were also included. A standardized pretested questionnaire addressed the following issues: socioeconomic characteristics, type of insects consumed and frequency of consumption, reasons and trends in consumption as well as reports on side effects, over the last 10 years. RESULTS: A total of 1059 adults (Sex ratio F/M: 1.2, 30 ethnic groups), and 256 vendors were enrolled. A total of 1025 (96.8%) lay people were currently insect consumers, 135 (13.0%) daily or weekly consumers, and 322 (31.1%) consumed several times per month. For the majority (575, 55.6%) the consumption was infrequent (less than a few times per year) and only 22 (2%) had never eaten insects. Consumption started in childhood. Insect availability was seasonal (670, 63.2%) and respondents would have eaten more insects, if they had been more available (919, 86.7%). Hmong and Leu ethnic groups had significantly lower consumption levels than the general population. Eggs of weaver ants, short-tailed crickets, crickets, grasshoppers, and cicadas were the top 5 insects consumed. Consumption had decreased in the last decade, mostly due to less availability (869; 84.0%) and change of life (29; 5.5%). Of 1059, 80 (7.5%) reported allergy problems and 106 (10.0%) reported some use in traditional medicine. A total of 874 (82.6%) were regular collectors. Insect vendors (Sex ratio F/M: 5.3) were also collectors (185; 72.2%). They dedicated a mean time of 4.7 hours during the last harvesting period. The majority sold insects at markets (141, 55.0%). They had earned, on average, USD 6.0 the day before. Five insects (weaver ant eggs; bamboo worms; short-tailed crickets; crickets; wasps) represented 85% of the market. CONCLUSION: Entomophagy is general in Laos, and well accepted despite a decreasing trend in consumption over the last decade. Its contribution to the Lao diet is limited to a minority of frequent consumers. Income through insect sales benefits mostly women. Consumption varies according to ethnicity, residence and season. Development of insect farming is still at an early stage. It could however increase availability of insects and contribute to the generation of income.

Road traffic injuries in northern Laos: trends and risk factors of an underreported public health problem.

OBJECTIVES: Road traffic injuries (RTI) have become a leading cause for admissions at Luang Namtha Provincial Hospital (LNPH) in rapidly developing northern Laos. Objectives were to investigate trends, risk factors and better estimates of RTI. METHODS: Repeated annual surveys were conducted with structured questionnaires among all RTI patients at LNPH from 2007 to 2011. Hospital and police data were combined by capture-recapture method. RESULTS: The majority of 1074 patients were young [median 22 years (1-88)], male (68%), motorcyclists (76%), drove without licence (85%) and without insurance (95%). Most accidents occurred during evenings and Lao New Year. Serious motorbike injuries were associated with young age (1-15 years), male sex (OR 2.2, 95% CI 1.1-4.6) and drivers (OR 2.1, 95% CI 1.1-4.3); more serious head injuries with alcohol consumption (OR 2.5, 95% CI 1.7-3.7), male sex (OR 2.3, 95% CI 1.4-3.7) and no helmet use (OR 2.0, 95% CI 1.2-3.4). No helmet use was associated with young age, time period, pillion passengers (OR 2.7, 95% CI 1.6-4.7), alcohol (OR 1.9, 95% CI 1.2-2.8) and no driver license (OR 2.0; 95% CI 1.1-3.4). Main reasons not to wear helmets were not possessing one, and being pillion passenger. Capture-recapture analysis showed four times higher RTI estimates than officially reported. Mortality rate was 11.6/100.000 population (95% CI 5.1-18.1/100.000). CONCLUSIONS: RTI were substantially underestimated. Combining hospital with police data can provide better estimates in resource-limited settings. Preventive programmes and law enforcement have to target male drivers, alcohol, licensing and helmet use, especially among children and pillion passengers. Increased efforts are needed during evening time and special festivals.

Gaps between research and public health priorities in low income countries: evidence from a systematic literature review focused on Cambodia.

BACKGROUND: Evidence-based public health requires that research provides policymakers with reliable and accessible information reflecting the disease threats. We described the scientific production of research in Cambodia and assessed to what extent it provides appropriate insights and implications for practice to guide health policymakers and managers and knowledge relevant for translation. METHODS: We conducted a systematic review of scientific articles published on biomedical research in Cambodia. Regression analysis assessed the trends over time and factors associated with actionable messages in the articles' abstracts. RESULTS: From 2000 to 2012, 628 articles were published in 237 journals with a significant increase over time (from 0.6/million population to 5.9/million population, slope coefficient 7.6, 95% CI 6.5-8.7, p < 0.001). Most publications on diseases addressed communicable diseases (n = 410, 65.3%). Non-communicable diseases (NCD) were under-addressed (7.7% of all publications) considering their burden (34.5% of the disease burden). Of all articles, 67.8% reported descriptive studies and 4.3% reported studies with a high level of evidence; 27.4% of studies were led by an institution based in Cambodia. Factors associated with an actionable message (n = 73, 26.6%) were maternal health (OR 3.08, 95% CI 1.55-6.13, p = 0.001), the first author's institution being Cambodian (OR 1.78, 95% CI 1.06-2.98, p = 0.02) and a free access to full article (OR 3.07, 95% CI 1.08-8.70, p = 0.03). Of all articles, 87% (n = 546) were accessible in full text from Cambodia. CONCLUSIONS: Scientific publications do not fully match with health priorities. Gaps remain regarding NCD, implementation studies, and health system research. A health research agenda would help align research with health priorities. We recommend 1) that the health authorities create an online repository of research findings with abstracts in the local language; 2) that academics emphasize the importance of research in their university teaching; and 3) that the researcher teams involve local researchers and that they systematically provide a translation of their abstracts upon submission to a journal. We conclude that building the bridge between research and public health requires a willful, comprehensive strategy rather than relying solely only publications.

The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data.

BACKGROUND: Artesunate-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. METHODS: Individual 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. RESULTS: Forty-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 < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites. CONCLUSIONS: There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.

Beriberi (thiamine deficiency) and high infant mortality in northern Laos.

BACKGROUND: Infantile beriberi (thiamine deficiency) occurs mainly in infants breastfed by mothers with inadequate intake of thiamine, typically among vulnerable populations. We describe possible and probable cases of infantile thiamine deficiency in northern Laos. METHODOLOGY/PRINCIPAL FINDINGS: Three surveys were conducted in Luang Namtha Province. First, we performed a retrospective survey of all infants with a diagnosis of thiamine deficiency admitted to the 5 hospitals in the province (2007-2009). Second, we prospectively recorded all infants with cardiac failure at Luang Namtha Hospital. Third, we further investigated all mothers with infants (1-6 months) living in 22 villages of the thiamine deficiency patients' origin. We performed a cross-sectional survey of all mothers and infants using a pre-tested questionnaire, physical examination and squat test. Infant mortality was estimated by verbal autopsy. From March to June 2010, four suspected infants with thiamine deficiency were admitted to Luang Namtha Provincial hospital. All recovered after parenteral thiamine injection. Between 2007 and 2009, 54 infants with possible/probable thiamine deficiency were diagnosed with acute severe cardiac failure, 49 (90.2%) were cured after parenteral thiamine; three died (5.6%). In the 22 villages, of 468 live born infants, 50 (10.6%, 95% CI: 8.0-13.8) died during the first year. A peak of mortality (36 deaths) was reported between 1 and 3 months. Verbal autopsy suggested that 17 deaths (3.6%) were due to suspected infantile thiamine deficiency. Of 127 mothers, 60 (47.2%) reported edema and paresthesia as well as a positive squat test during pregnancy; 125 (98.4%) respected post-partum food avoidance and all ate polished rice. Of 127 infants, 2 (1.6%) had probable thiamine deficiency, and 8 (6.8%) possible thiamine deficiency. CONCLUSION: Thiamine deficiency may be a major cause of infant mortality among ethnic groups in northern Laos. Mothers' and children's symptoms are compatible with thiamine deficiency. The severity of this nutritional situation requires urgent attention in Laos.

Improving the management of dysglycemia in children in the developing world.

Improving the availability of point-of-care (POC) diagnostics for glucose is crucial in resource-constrained settings (RCS). Both hypo and hyperglycemia have an appreciable frequency in the tropics and have been associated with increased risk of deaths in pediatrics units. However, causes of dysglycemia, including hyperglycemia, are numerous and insufficiently documented in RCS. Effective glycemic control with glucose infusion and/or intensive insulin therapy can improve clinical outcomes in western settings. A non-invasive way for insulin administration is not yet available for hyperglycemia. We documented a few causes and developed simple POC treatment of hypoglycemia in RCS. We showed the efficacy of sublingual sugar in two clinical trials. Dextrose gel has been recently tested for neonate mortality. This represents an interesting alternative that should be compared with sublingual sugar in RCS. New studies had to be done to document dysglycemia mechanism, frequency and morbid-mortality, and safe POC treatment in the tropics.

Perceived stigma by children on antiretroviral treatment in Cambodia.

BACKGROUND: HIV-related stigma diminishes the quality of life of affected patients. Little is known about perceived and enacted stigma of HIV-infected children in resources-limited settings. We documented the prevalence of perceived stigma and associated factors associated among children on antiretroviral therapy (ART) at a referral hospital in Cambodia. METHODS: After informed consent, a standardized pre-tested 47-item questionnaire was confidentially administered to consecutive children (7 to 15 years) or their guardians if the child was 18 months to 6 years, during their routine ART visits. The questionnaire explored the sociodemographics of the child and the parents, HIV history, adherence to ART, tolerance of ART and perceived stigma. Associations between perceived stigma and the children's characteristics were measured by bivariate and multivariate analyses. RESULTS: Of 183 children, 101 (55.2%) had lost at least one and 45 (24.6%) both parents; 166 (90.7%) went to school. Of 183 children (female: 84, 45.9%, median age 7.0 years, interquartile range: 2.0-9.6), 79 (43.2%) experienced perceived stigma, including rejection by others (26.8%), no invitations to social activities (18.6%) and exclusion from games (14.2%). A total of 43 (23.5%) children were fearful of their disease and 61 (53.9%) of 113 older than 6 years reported knowledge of their HIV status. Of 136 children over five years and eligible for education, 7 (3.8%) could not go to school due to perceived stigma. Incomplete adherence to ART was reported for 17 (9.2%) children. In multivariate analysis, school attendance (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 2.0-7.9) and income of less than one dollar per person per day (OR: 2.2, 95% CI: 1.1-4.5) were associated with perceived stigma. Conversely, receipt of social support (OR: 0.4, 95% CI 0.2-0.9) was associated with lower risk of perceived stigma. CONCLUSION: Perceived stigma in pediatric ART patients remains a significant issue in Cambodia. Psychological support and interventions should be developed in hospitals, schools, and underprivileged communities to prevent HIV-related stigma for affected children.

Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia.

INTRODUCTION: In resource limited settings, patients entering an antiretroviral therapy (ART) program comprise ART naive and ART pre-treated patients who may show differential virological outcomes. METHODS: This retrospective study, conducted in 2010-2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia) assessed virological failure (VF) rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL) was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF) (>1,000 copies/ml) underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms. RESULTS: On a total of 209 patients, 164 (78.4%) were naive and 45 (21.5%) were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30-194) and 279 cells/mm3 (IQR: 103-455) (p<0.001), respectively. Twenty seven patients (12.9%) exhibited VF (95% CI: 8.6-18.2%), including 10 naive (10/164, 6.0%) and 17 pre-treated (17/45, 37.8%) patients (p<0.001). Among these viremic patients, twenty-two (81.4%) were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3%) harbored ≥1 drug resistance mutations (DRMs) whereas 3 (all belonging to pre-treated patients) harbored wild-types viruses. The most frequent DRMs were M184V (86.3%), K103N (45.5%) and thymidine analog mutations (TAMs) (40.9%). Two (13.3%) pre-treated patients harbored viruses that showed a multi-nucleos(t)ide resistance including Q151M, K65R, E33A/D, E44A/D mutations. CONCLUSION: In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre-treated patients infection should be considered as well.

Knowledge translation: a case study on pneumonia research and clinical guidelines in a low- income country.

BACKGROUND: The process and effectiveness of knowledge translation (KT) interventions targeting policymakers are rarely reported. In Cambodia, a low-income country (LIC), an intervention aiming to provide evidence-based knowledge on pneumonia to health authorities was developed to help update pediatric and adult national clinical guidelines. Through a case study, we assessed the effectiveness of this KT intervention, with the goal of identifying the barriers to KT and suggest strategies to facilitate KT in similar settings. METHODS: An extensive search for all relevant sources of data documenting the processes of updating adult and pediatric pneumonia guidelines was done. Documents included among others, reports, meeting minutes, and email correspondences. The study was conducted in successive phases: an appraisal of the content of both adult and pediatric pneumonia guidelines; an appraisal of the quality of guidelines by independent experts, using the AGREE-II instrument; a description and modeling of the KT process within the guidelines updating system, using the Unified Modeling Language (UML) tools 2.2; and the listing of the barriers and facilitators to KT we identified during the study. RESULTS: The first appraisal showed that the integration of the KT key messages in pediatric and adult guidelines varied with a better efficiency in the pediatric guidelines. The overall AGREE-II quality assessments scored 37% and 44% for adult and pediatric guidelines, respectively. Scores were lowest for the domains of 'rigor of development' and 'editorial independence.' The UML analysis highlighted that time frames and constraints of the involved stakeholders greatly differed and that there were several missed opportunities to translate on evidence into the adult pneumonia guideline. Seventeen facilitating factors and 18 potential barriers to KT were identified. Main barriers were related to the absence of a clear mandate from the Ministry of Health for the researchers and to a lack of synchronization between knowledge production and policy-making. CONCLUSIONS: Study findings suggest that stakeholders, both researchers and policy makers planning to update clinical guidelines in LIC may need methodological support to overcome the expected barriers.