Glycemic control during TB treatment among Filipinos: The Starting Anti-Tuberculosis Treatment Cohort Study.

Poor TB treatment outcomes are observed in patients with type 2 diabetes mellitus (DM) comorbidity and glycemic control throughout treatment may play a role. The objective of this study was to investigate glycemic control longitudinally among Filipino adults undergoing TB treatment using mixed-effects linear and logistic regression. Analyses were conducted in 188 DM-TB patients out of 901 enrolled in the Starting Anti-TB Treatment (St-ATT) cohort, with a median baseline glycosylated hemoglobin (HbA1c) of 8.2% (range 4.5-13.3%). Previous versus new DM diagnosis was associated with higher mean HbA1c (worse glycemic control) during treatment, with a smaller effect amongst those with central obesity (coefficient 0.80, 95% confidence interval [CI] 0.26, 1.57, P = 0.043) than amongst those without central obesity (coefficient 3.48, 95% CI 2.16, 4.80, P<0.001). In those with a new DM diagnosis, central obesity was associated with higher blood glucose (coefficient 1.62, 95% CI 0.72, 2.53, P = 0.009). Of 177 participants with ≥2 HbA1c results, 40% had uncontrolled glycemia (≥2 HbA1c results ≥8%). Of 165 participants with ≥3 HbA1c results, 29.9% had consistently-controlled glycemia, 15.3% had initially-uncontrolled glycemia, and 18.6% had consistently-uncontrolled glycemia. Previous versus new DM diagnosis and glucose-lowering medication use versus no use were associated with having uncontrolled versus controlled glycemia (adjusted odds ratio [aOR] 2.50 95%CI 1.61, 6.05, P = 0.042; aOR 4.78 95% CI 1.61,14.23, P<0.001) and more likely to have consistently-uncontrolled versus consistently-controlled glycemia (adjusted relative risk ratio [aRRR] 5.14 95% CI 1.37, 19.20, P = 0.015; aRRR 10.24 95% CI 0.07, 0.95, P = 0.003). Relapse cases of TB were less likely than new cases to have uncontrolled (aOR 0.20 95%CI 0.06, 0.63, P = 0.031) or consistently-uncontrolled (aRRR 0.25 95%CI 0.07, 0.95, P = 0.042) versus controlled glycemia. Those with long-term DM, suggested by previous diagnosis, glucose-lowering medication use and possibly central obesity, may require additional support to manage blood glucose during TB treatment.

Costs incurred by people with co-morbid tuberculosis and diabetes and their households in the Philippines.

OBJECTIVE: Diabetes is a risk factor for TB mortality and relapse. The Philippines has a high TB incidence with co-morbid diabetes. This study assessed the pre- and post-TB diagnosis costs incurred by people with TB and diabetes (TB-DM) and their households in the Philippines. METHODS: Longitudinal data was collected for costs, income, and coping mechanisms of TB-affected households in Negros Occidental and Cebu, the Philippines. Data collection was conducted four times during TB treatment. The data collection tools were developed by adapting WHO's cross-sectional questionnaire in the Tuberculosis Patient Cost Surveys: A Handbook into a longitudinal study design. Demographic and clinical characteristics, self-reported household income, number of facility visits, patient costs, the proportion of TB-affected households facing catastrophic costs due to TB (>20% of annual household income before TB), coping mechanisms, and social support received were compared by diabetes status at the time of TB diagnosis. RESULTS: 530 people with TB were enrolled in this study, and 144 (27.2%) had TB-DM based on diabetes testing at the time of TB diagnosis. 75.4% of people with TB-DM were more than 45 years old compared to 50.3% of people with TB-only (p<0.001). People with TB-DM had more frequent visits for TB treatment (120 vs 87 visits, p = 0.054) as well as for total visits for TB-DM treatment (129 vs 88 visits, p = 0.010) compared to those with TB-only. There was no significant difference in the proportion of TB-affected households facing catastrophic costs between those with TB-DM (76.3%) and those with TB-only (68.7%, p = 0.691). CONCLUSION: People with TB-DM in the Philippines face extensive health service use. However, this does not translate into substantial differences in the incidence of catastrophic cost. Further study is required to understand the incidence of catastrophic costs due to diabetes-only in the Philippines.

Long-term health after Severe Acute Malnutrition in children and adults- the role of the Pancreas (SAMPA): Protocol.

Background: Prenatal growth retardation may increase the risk of later chronic non-communicable diseases (NCDs), including diabetes; however, long-term effects of wasting malnutrition in childhood or adulthood are less studied. Pancreatic exocrine and endocrine functions, both critical for nutrition and NCD aetiology, may not fully recover following malnutrition. However, the evidence and mechanistic information is piecemeal. We hypothesise that wasting malnutrition at any age has long-term detrimental effects on endocrine and exocrine pancreatic structure and function. Methods: The SAMPA international research programme will assess pancreatic structure and function in 3700 participants from ongoing observational nutrition cohorts, two adolescent and four adult, in Zambia, Tanzania, Philippines, and India. Pancreas size, structure, and calcification will be assessed by ultrasound and computed tomography (CT) scan; exocrine function by faecal elastase and serum lipase; and endocrine function by haemoglobin A1c (HbA1c) and blood glucose, insulin and C-peptide concentrations during an oral glucose tolerance test (OGTT). In-depth hormonal analyses of incretins, glucagon, proinsulin and trypsinogen during OGTT and intravenous glucose tolerance tests will be done in subsets of adult participants. Pancreatic size and function outcomes will be compared between people with and without prior wasting malnutrition. Analyses will investigate effect modification by sex, current age, time since malnutrition, current body mass index and dietary patterns. Mathematical modelling of OGTT data will be used to estimate the relative contribution to glucose dysregulation of decreased insulin production, changes in insulin clearance and increased insulin resistance. Proinsulin/insulin ratio will be analysed in archived samples from the Tanzanian cohort using a nested case-control design to investigate whether abnormal values precede diabetes. Conclusions: SAMPA, a large-scale multi-centre research programme using data from people with or without prior wasting malnutrition to assess several aspects of pancreatic phenotype, will provide coherent evidence for future policies and programmes for malnutrition and diabetes.

Experiences, challenges and looking to the future in a clinical tuberculosis cohort in the time of COVID-19 in the Philippines.

A cohort study of Filipino tuberculosis patients is currently undergoing data collection amidst the coronavirus disease 2019 pandemic. In this article we present the current experiences, challenges and obstacles of our team during this period as we attempt to fulfil our roles and responsibilities in Metro Manila, Cebu and Negros Occidental in the Philippines. Each site had different lockdown restrictions and experienced problems to different degrees. The underlying themes were similar, covering the supply chain, mobility, communication, physical and mental health and disruption of health services due to reallocation of staff. While we maximized the use of mobile devices, logistical challenges remained. Institutional support for the field teams, creative problem solving and resilience are required to adapt in a rapidly changing environment.

Patterns of non-communicable comorbidities at start of tuberculosis treatment in three regions of the Philippines: The St-ATT cohort.

Diabetes and undernutrition are common risk factors for tuberculosis (TB), associated with poor treatment outcomes and exacerbated by TB. Limited data exist describing patterns and risk factors of multiple comorbidities in persons with TB. Nine-hundred participants (69.6% male) were enrolled in the Starting Anti-TB Treatment (St-ATT) cohort, including 133 (14.8%) initiating treatment for multi-drug resistant TB (MDR-TB). Comorbidities were defined as: diabetes, HbA1c ≥6.5% and/or on medication; hypertension, systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg and/or on medication; anaemia (moderate/severe), haemoglobin <11g/dL; and, undernutrition (moderate/severe) body-mass-index <17 kg/m2. The most common comorbidities were undernutrition 23.4% (210/899), diabetes 22.5% (199/881), hypertension 19.0% (164/864) and anaemia 13.5% (121/899). Fifty-eight percent had ≥1 comorbid condition (496/847), with 17.1% having ≥2; most frequently diabetes and hypertension (N = 57, 6.7%). Just over half of diabetes (54.8%) and hypertension (54.9%) was previously undiagnosed. Poor glycemic control in those on medication (HbA1c≥8.0%) was common (N = 50/73, 68.5%). MDR-TB treatment was associated with increased odds of diabetes (Adjusted odds ratio (AOR) = 2.48, 95% CI: 1.55-3.95); but decreased odds of hypertension (AOR = 0.55, 95% CI: 0.39-0.78). HIV infection was only associated with anaemia (AOR = 4.51, 95% CI: 1.01-20.1). Previous TB treatment was associated with moderate/severe undernutrition (AOR = 1.98, 95% CI: 1.40-2.80), as was duration of TB-symptoms before starting treatment and household food insecurity. No associations for sex, alcohol or tobacco use were observed. MDR-TB treatment was marginally associated with having ≥2 comorbidities (OR = 1.52, 95% CI: 0.97-2.39). TB treatment programmes should plan for large proportions of persons requiring diagnosis and management of comorbidities with the potential to adversely affect TB treatment outcomes and quality of life. Dietary advice and nutritional management are components of comprehensive care for the above conditions as well as TB and should be included in planning of patient-centred services.

Patterns and predictors of co-morbidities in Tuberculosis: A cross-sectional study in the Philippines.

Diabetes and undernutrition are common risk factors for TB, associated with poor treatment outcomes and exacerbated by TB. We aimed to assess non-communicable multimorbidity (co-occurrence of two or more medical conditions) in Filipino TB outpatients, focusing on malnutrition and diabetes. In a cross-sectional study, 637 adults (70% male) from clinics in urban Metro Manila (N = 338) and rural Negros Occidental (N = 299) were enrolled. Diabetes was defined as HbA1c of ≥6.5% and/or current diabetes medication. Study-specific HIV screening was conducted. The prevalence of diabetes was 9.2% (54/589, 95%CI: 7.0-11.8%) with 52% newly diagnosed. Moderate/severe undernutrition (body mass index (BMI) <17 kg/2) was 20.5% (130/634, 95%CI: 17.4-23.9%). Forty percent of participants had at least one co-morbidity (diabetes, moderate/severe undernutrition or moderate/severe anaemia (haemoglobin <11 g/dL)). HIV infection (24.4%, 74/303) was not associated with other co-morbidities (but high refusal in rural clinics). Central obesity assessed by waist-to-hip ratio was more strongly associated with diabetes (Adjusted Odds Ratio (AOR) = 6.16, 95%CI: 3.15-12.0) than BMI. Undernutrition was less common in men (AOR = 0.44, 95%CI: 0.28-0.70), and associated with previous history of TB (AOR = 1.97, 95%CI: 1.28-3.04) and recent reduced food intake. The prevalence of multimorbidity was high demonstrating a significant unmet need. HIV was not a risk factor for increased non-communicable multimorbidity.

Fortification of rice with vitamins and minerals for addressing micronutrient malnutrition.

BACKGROUND: Rice fortification with vitamins and minerals has the potential to increase the nutrition in rice-consuming countries where micronutrient deficiencies exist. Globally, 490 million metric tonnes of rice are consumed annually. It is the dominant staple food crop of around three billion people. OBJECTIVES: To determine the benefits and harms of rice fortification with vitamins and minerals (iron, vitamin A, zinc or folic acid) on micronutrient status and health-related outcomes in the general population. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and 16 other databases all up to 10 December 2018. We searched ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (ICTRP) on 10 December 2018. SELECTION CRITERIA: We included randomised and quasi-randomised trials (with either individual or cluster randomisation) and controlled before-and-after studies. Participants were populations older than two years of age (including pregnant women) from any country. The intervention was rice fortified with at least one micronutrient or a combination of several micronutrients (iron, folic acid, zinc, vitamin A or other vitamins and minerals) compared with unfortified rice or no intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently screened studies and extracted data. MAIN RESULTS: We included 17 studies (10,483 participants) and identified two ongoing studies. Twelve included studies were randomised-controlled trials (RCTs), with 2238 participants after adjusting for clustering in two cluster-RCTs, and five were non-randomised studies (NRS) with four controlled before-and-after studies and one cross-sectional study with a control (8245 participants). Four studies were conducted in India, three in Thailand, two in the Philippines, two in Brazil, one each in Bangladesh, Burundi, Cambodia, Indonesia, Mexico and the USA. Two studies involved non-pregnant, non-lactating women and 10 involved pre-school or school-age children. All 17 studies reported fortification with iron. Of these, six studies fortified rice with iron only; 11 studies had other micronutrients added (iron, zinc and vitamin A, and folic acid). One study had one arm each with vitamin A alone and carotenoid alone. Elemental iron content ranged from 0.2 to 112.8 mg/100 g uncooked rice given for a period varying from two weeks to 48 months. Thirteen studies did not clearly describe either sequence generation or allocation concealment. Eleven studies had a low attrition rate. There was no indication of selective reporting in the studies. We considered two RCTs at low overall risk of bias and 10 at high overall risk of bias. One RCT was at high or unclear risk of bias for most of the domains. All controlled before-and-after studies had a high risk or unclear risk of bias in most domains. The included studies were funded by Government, private and non-governmental organisations, along with other academic institutions. The source of funding does not appear to have altered the results. We used the NRS in the qualitative synthesis but we excluded them from the quantitative analysis and review conclusions since they provided mostly contextual information and limited quantitative information. Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added) Fortification of rice with iron (alone or in combination with other micronutrients) may make little or no difference in the risk of having anaemia (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.54 to 0.97; I2 = 74%; 7 studies, 1634 participants; low-certainty evidence) and may reduce the risk of iron deficiency (RR 0.66, 95% CI 0.51 to 0.84; 8 studies, 1733 participants; low-certainty evidence). Rice fortification may increase mean haemoglobin (mean difference (MD) 1.83, 95% CI 0.66 to 3.00; I2 = 54%; 11 studies, 2163 participants; low-certainty evidence) and it may make little or no difference to vitamin A deficiency (with vitamin A as one of the micronutrients in the fortification arm) (RR 0.68, 95% CI 0.36 to 1.29; I2 = 37%; 4 studies, 927 participants; low-certainty evidence). One study reported that fortification of rice (with folic acid as one of the micronutrients) may improve serum or plasma folate (nmol/L) (MD 4.30, 95% CI 2.00 to 6.60; 215 participants; low-certainty evidence). One study reported that fortification of rice with iron alone or with other micronutrients may slightly increase hookworm infection (RR 1.78, 95% CI 1.18 to 2.70; 785 participants; low-certainty evidence). We are uncertain about the effect of fortified rice on diarrhoea (RR 3.52, 95% CI 0.18 to 67.39; 1 study, 258 participants; very low-certainty evidence). Rice fortified with vitamin A alone or in combination with other micronutrients versus unfortified rice (no micronutrients added) One study had one arm providing fortified rice with vitamin A only versus unfortified rice. Fortification of rice with vitamin A (in combination with other micronutrients) may increase mean haemoglobin (MD 10.00, 95% CI 8.79 to 11.21; 1 study, 74 participants; low-certainty evidence). Rice fortified with vitamin A may slightly improve serum retinol concentration (MD 0.17, 95% CI 0.13 to 0.21; 1 study, 74 participants; low-certainty evidence). No studies contributed data to the comparisons of rice fortification versus no intervention. The studies involving folic acid and zinc also involved iron in the fortification arms and hence we reported them as part of the first comparison. AUTHORS' CONCLUSIONS: Fortification of rice with iron alone or in combination with other micronutrients may make little or no difference in the risk of having anaemia or presenting iron deficiency and we are uncertain about an increase in mean haemoglobin concentrations in the general population older than 2 years of age. Fortification of rice with iron and other micronutrients such as vitamin A or folic acid may make little or no difference in the risk of having vitamin A deficiency or on the serum folate concentration. There is limited evidence on any adverse effects of rice fortification.

Fortification of staple foods with vitamin A for vitamin A deficiency.

BACKGROUND: Vitamin A deficiency is a significant public health problem in many low- and middle-income countries, especially affecting young children, women of reproductive age, and pregnant women. Fortification of staple foods with vitamin A has been used to increase vitamin A consumption among these groups. OBJECTIVES: To assess the effects of fortifying staple foods with vitamin A for reducing vitamin A deficiency and improving health-related outcomes in the general population older than two years of age. SEARCH METHODS: We searched the following international databases with no language or date restrictions: Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library; MEDLINE and MEDLINE In Process OVID; Embase OVID; CINAHL Ebsco; Web of Science (ISI) SCI, SSCI, CPCI-exp and CPCI-SSH; BIOSIS (ISI); POPLINE; Bibliomap; TRoPHI; ASSIA (Proquest); IBECS; SCIELO; Global Index Medicus - AFRO and EMRO; LILACS; PAHO; WHOLIS; WPRO; IMSEAR; IndMED; and Native Health Research Database. We also searched clinicaltrials.gov and the International Clinical Trials Registry Platform to identify ongoing and unpublished studies. The date of the last search was 19 July 2018. SELECTION CRITERIA: We included individually or cluster-randomised controlled trials (RCTs) in this review. The intervention included fortification of staple foods (sugar, edible oils, edible fats, maize flour or corn meal, wheat flour, milk and dairy products, and condiments and seasonings) with vitamin A alone or in combination with other vitamins and minerals. We included the general population older than two years of age (including pregnant and lactating women) from any country. DATA COLLECTION AND ANALYSIS: Two authors independently screened and assessed eligibility of studies for inclusion, extracted data from included studies and assessed their risk of bias. We used standard Cochrane methodology to carry out the review. MAIN RESULTS: We included 10 randomised controlled trials involving 4455 participants. All the studies were conducted in low- and upper-middle income countries where vitamin A deficiency was a public health issue. One of the included trials did not contribute data to the outcomes of interest.Three trials compared provision of staple foods fortified with vitamin A versus unfortified staple food, five trials compared provision of staple foods fortified with vitamin A plus other micronutrients versus unfortified staple foods, and two trials compared provision of staple foods fortified with vitamin A plus other micronutrients versus no intervention. No studies compared staple foods fortified with vitamin A alone versus no intervention.The duration of interventions ranged from three to nine months. We assessed six studies at high risk of bias overall. Government organisations, non-governmental organisations, the private sector, and academic institutions funded the included studies; funding source does not appear to have distorted the results.Staple food fortified with vitamin A versus unfortified staple food We are uncertain whether fortifying staple foods with vitamin A alone makes little or no difference for serum retinol concentration (mean difference (MD) 0.03 µmol/L, 95% CI -0.06 to 0.12; 3 studies, 1829 participants; I² = 90%, very low-certainty evidence). It is uncertain whether vitamin A alone reduces the risk of subclinical vitamin A deficiency (risk ratio (RR) 0.45, 95% CI 0.19 to 1.05; 2 studies; 993 participants; I² = 33%, very low-certainty evidence). The certainty of the evidence was mainly affected by risk of bias, imprecision and inconsistency.It is uncertain whether vitamin A fortification reduces clinical vitamin A deficiency, defined as night blindness (RR 0.11, 95% CI 0.01 to 1.98; 1 study, 581 participants, very low-certainty evidence). The certainty of the evidence was mainly affected by imprecision, inconsistency, and risk of bias.Staple foods fortified with vitamin A versus no intervention No studies provided data for this comparison.Staple foods fortified with vitamin A plus other micronutrients versus same unfortified staple foods Fortifying staple foods with vitamin A plus other micronutrients may not increase the serum retinol concentration (MD 0.08 µmol/L, 95% CI -0.06 to 0.22; 4 studies; 1009 participants; I² = 95%, low-certainty evidence). The certainty of the evidence was mainly affected by serious inconsistency and risk of bias.In comparison to unfortified staple foods, fortification with vitamin A plus other micronutrients probably reduces the risk of subclinical vitamin A deficiency (RR 0.27, 95% CI 0.16 to 0.49; 3 studies; 923 participants; I² = 0%; moderate-certainty evidence). The certainty of the evidence was mainly affected by serious risk of bias.Staple foods fortified with vitamin A plus other micronutrients versus no interventionFortification of staple foods with vitamin A plus other micronutrients may increase serum retinol concentration (MD 0.22 µmol/L, 95% CI 0.15 to 0.30; 2 studies; 318 participants; I² = 0%; low-certainty evidence). When compared to no intervention, it is uncertain whether the intervention reduces the risk of subclinical vitamin A deficiency (RR 0.71, 95% CI 0.52 to 0.98; 2 studies; 318 participants; I² = 0%; very low-certainty evidence) . The certainty of the evidence was affected mainly by serious imprecision and risk of bias.No trials reported on the outcomes of all-cause morbidity, all-cause mortality, adverse effects, food intake, congenital anomalies (for pregnant women), or breast milk concentration (for lactating women). AUTHORS' CONCLUSIONS: Fortifying staple foods with vitamin A alone may make little or no difference to serum retinol concentrations or the risk of subclinical vitamin A deficiency. In comparison with provision of unfortified foods, provision of staple foods fortified with vitamin A plus other micronutrients may not increase serum retinol concentration but probably reduces the risk of subclinical vitamin A deficiency.Compared to no intervention, staple foods fortified with vitamin A plus other micronutrients may increase serum retinol concentration, although it is uncertain whether the intervention reduces the risk of subclinical vitamin A deficiency as the certainty of the evidence has been assessed as very low.It was not possible to estimate the effect of staple food fortification on outcomes such as mortality, morbidity, adverse effects, congenital anomalies, or breast milk vitamin A, as no trials included these outcomes.The type of funding source for the studies did not appear to distort the results from the analysis.

Epidemiologic Study of Blastocystis Infection in an Urban Community in the Philippines.

Blastocystis has been considered as the most common intestinal parasite in humans and has an augmented impact on public health. However, the prevalence of this parasite in the Philippines has not been determined. To contribute to a better understanding of the epidemiology of this infection, a cross-sectional study aimed at providing the first documented data on the prevalence and correlates, sociodemographic factors, hygiene practices, source of water supply, and dog ownership, associated with Blastocystis infection was carried out in randomly selected communities at Pateros, Metro Manila. Fecal samples from respondents were collected and cultured in diphasic agar medium for 3-7 days and examined using light microscopy. Of the 1,271 respondents, 12.98% (95% CI: 11.13-14.83) were detected positive for Blastocystis. Among the correlates of Blastocystis infection, dog ownership was found significantly associated as confirmed by multivariate analysis. Therefore, this factor should be considered in information to create awareness about Blastocystis and to prevent and control Blastocystis infection in particular and diarrheal diseases in general. Further studies using molecular approaches to distinguish subtype and to determine genetic characteristics of isolates from humans and dogs are recommended to analyze their relationship and provide more conclusive evidence of cross-transmission.

New endemic foci of schistosomiasis infections in the Philippines.

Schistosomiasis affects 28 provinces in the Philippines found along the southeastern part where there is continuous rainfall throughout the year. In 2002 and 2005 respectively, two new endemic foci were reported in the northernmost (Gonzaga, Cagayan) and central (Calatrava, Negros Occidental) parts of the country. This study conducted in March 2008-March 2009 confirmed the presence of the disease by determining its prevalence using four diagnostic tests - Kato-Katz, circumoval precipitin test (COPT), ELISA and ultrasonography. Oncomelania hupensis quadrasi was identified through snail surveys conducted in possible snail habitats in the seven new endemic villages. Animal surveys through stool examination confirmed the presence of schistosomiasis infection in animals in Gonzaga but not in Calatrava. Compared to Calatrava, Gonzaga demonstrated markedly higher prevalence of schistosomiasis using all four diagnostic methods. Proximity of snail habitats to human habitation including higher snail density and snail infection rate could be responsible for the high prevalence. Snail sites were more widespread in Gonzaga whereas those in Calatrava were confined only in areas not frequented by the general population except by farmers. GIS maps showing spatial distribution of snails in Gonzaga and Calatrava indicated differences in elevation among the snail sites. It is hypothesized that the snail intermediate host has been in these sites for sometime but discovered only lately. Migration of people from endemic provinces into Gonzaga and Calatrava brought in cases and in the presence of snail intermediate hosts, emergence of disease was just a matter of time.

Development of a loop-mediated isothermal amplification assay for detection of Trichomonas vaginalis.

A loop-mediated isothermal amplification (LAMP) assay targeting the 2-kbp repeated DNA species-specific sequence was developed for detection of Trichomonas vaginalis, the causative agent of trichomoniasis. The analytical sensitivity and specificity of the LAMP assay were evaluated using pooled genital swab and urine specimens, respectively, spiked with T. vaginalis trophozoites. Genital secretion and urine did not inhibit the detection of the parasite. The sensitivity of the LAMP was 10-1000 times higher than the PCR performed. The detection limit of LAMP was 1 trichomonad for both spiked genital swab and urine specimens. Also, LAMP did not exhibit cross-reactivity with closely-related trichomonads, Trichomonas tenax and Pentatrichomonas hominis, and other enteric and urogenital microorganisms, Entamoeba histolytica, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. This is the first report of a LAMP assay for the detection of T. vaginalis and has prospective application for rapid diagnosis and control of trichomoniasis.

A randomized, controlled dose-finding Phase II study of the M72/AS01 candidate tuberculosis vaccine in healthy PPD-positive adults.

PURPOSE: In this dose-finding Phase II study (NCT00621322), we evaluated the safety and immunogenicity of different formulations of the candidate tuberculosis vaccine containing the M72 antigen (10/20/40 µg doses) and the liposome-based AS01 Adjuvant System. We aimed to select the lowest-dose combination of M72 and AS01 that was clinically well tolerated with immunogenicity comparable to that of the previously tested M72/AS01B (40 µg) candidate vaccine. METHODS: Healthy PPD-positive (induration 3-10 mm) adults (18-45 years) in The Philippines were randomized (4:4:4:4:1:1) to receive 2 injections, 1 month apart, of M72/AS01B (40 µg), M72/AS01E (10 µg), M72/AS01E (20 µg), M72/AS02D (10 µg), M72/Saline (40 µg) or AS01B alone, and were followed up for 6 months. AS01E and AS02D contain half the quantities of the immunostimulants present in AS01B. AS02D is an oil-in-water emulsion. Vaccine selection was based on the CD4(+) T-cell responses at 1 month post vaccination. RESULTS: All formulations had a clinically acceptable safety profile with no vaccine-related serious adverse events reported. Two vaccinations of each adjuvanted M72 vaccine induced M72-specific CD4(+) T-cell and humoral responses persisting at 6 months post vaccination. No responses were observed with AS01B alone. One month post second vaccination, CD4(+) T-cell responses induced by each of the three M72/AS01 vaccine formulations were of comparable magnitudes, and all were significantly higher than those induced by M72/AS02D (10 µg) and M72/Saline. CONCLUSIONS: The formulation with the lowest antigen and adjuvant dose, M72/AS01E (10 µg), fulfilled our pre-defined selection criteria and has been selected for further clinical development.

Slaving and release in co-infection control.

BACKGROUND: Animal and human infection with multiple parasite species is the norm rather than the exception, and empirical studies and animal models have provided evidence for a diverse range of interactions among parasites. We demonstrate how an optimal control strategy should be tailored to the pathogen community and tempered by species-level knowledge of drug sensitivity with use of a simple epidemiological model of gastro-intestinal nematodes. METHODS: We construct a fully mechanistic model of macroparasite co-infection and use it to explore a range of control scenarios involving chemotherapy as well as improvements to sanitation. RESULTS: Scenarios are presented whereby control not only releases a more resistant parasite from antagonistic interactions, but risks increasing co-infection rates, exacerbating the burden of disease. In contrast, synergisms between species result in their becoming epidemiologically slaved within hosts, presenting a novel opportunity for controlling drug resistant parasites by targeting co-circulating species. CONCLUSIONS: Understanding the effects on control of multi-parasite species interactions, and vice versa, is of increasing urgency in the advent of integrated mass intervention programmes.

Thymic function and T cell parameters in a natural human experimental model of seasonal infectious diseases and nutritional burden.

BACKGROUND: The study exploits a natural human experimental model of subsistence farmers experiencing chronic and seasonally modified food shortages and infectious burden. Two seasons existed, one of increased deprivation and infections (Jul-Dec), another of abundance and low infections (Jan-Jun); referred to as the hungry/high infection and harvest/low infection seasons respectively. Prior analysis showed a 10-fold excess in infectious disease associated mortality in young adults born in the hungry/high infection versus harvest/low infection season, and reduced thymic output and T cell counts in infancy. Here we report findings on the role of early life stressors as contributors to the onset of T cell immunological defects in later life. METHODS: We hypothesised that season of birth effects on thymic function and T cell immunity would be detectable in young adults since Kaplan-Meier survival curves indicated this to be the time of greatest mortality divergence. T cell subset analyses by flow-cytometry, sjTRECs, TCRVß repertoire and telomere length by PCR, were performed on samples from 60 males (18-23 y) selected to represent births in the hungry/high infection and harvest/low infection RESULTS: Total lymphocyte counts were normal and did not differ by birth season. CD3+ and CD4+ but not CD8+ counts were lower for those born during the hungry/high infection season. CD8+ telomere length also tended to be shorter. Overall, CD8+ TCRVß repertoire skewing was observed with 'public' expressions and deletions seen in TCRVß12/22 and TCRVß24, respectively but no apparent effect of birth season. CONCLUSIONS: We conclude that, although thymic function was unchanged, the CD4+ and CD3+ counts, and CD8+ telomere length results suggested that aspects of adult T cell immunity were under the influence of early life stressors. The endemicity of CMV and HBV suggested that chronic infections may modulate immunity through T cell repertoire development. The overall implications being that, this population is at an elevated risk of premature immunosenescence possibly driven by a combination of nutritional and infectious burden.

Home gardening is associated with Filipino preschool children's dietary diversity.

Dietary diversification through home gardening is a sustainable strategy that can address multiple micronutrient deficiencies. This cross-sectional study aimed to determine the association between home gardening and the dietary diversity of preschool-aged children. Households with children aged 2 to 5 years (n=200) were surveyed from Baras and Angono in the province of Rizal, Philippines in January 2008. Food security was determined based on the US Department of Agriculture Food Security Questionnaire. Dietary diversity score was based on the number of unique food groups consumed during the past 24 hours. The Student t test was performed to compare means between groups (households with gardens vs households without gardens) whereas proportions between groups were compared using Pearson's χ(2) analyses. Multiple linear regression was performed to model the adjusted regression coefficients for the quantitative outcome variables by exposure variable. Around 52.5% of children were from households with a fruit and/or vegetable garden. Children from households with gardens had higher dietary diversity scores whether using the all-inclusive dietary diversity score (6.12 vs 5.62; P=0.040) or applying a 10-g minimum intake for each food group (5.89 vs 5.37; P=0.044) compared with children who lived in homes without a garden. Children from households with gardens were significantly more likely to eat vegetables more frequently (χ(2)=9.06; P=0.029). The presence or absence of a garden was not significantly associated with food security. Having a home garden was positively associated with the child's diet diversity and with frequency of vegetable consumption. Households without gardens may benefit from interventions promoting gardens as a means to improve diet quality.

Physical activity, energy requirements, and adequacy of dietary intakes of older persons in a rural Filipino community.

BACKGROUND: Aging is a process associated with physiological changes such as in body composition, energy expenditure and physical activity. Data on energy and nutrient intake adequacy among elderly is important for disease prevention, health maintenance and program development. METHODS: This descriptive cross-sectional study was designed to determine the energy requirements and adequacy of energy and nutrient intakes of older persons living in private households in a rural Filipino community. Study participants were generally-healthy, ambulatory, and community living elderly aged 60-100 y (n = 98), 88 of whom provided dietary information in three nonconsecutive 24-hour food-recall interviews. RESULTS: There was a decrease in both physical activity and food intake with increasing years. Based on total energy expenditure and controlling for age, gender and socio-economic status, the average energy requirement for near-old (>or= 60 to < 65 y) males was 2074 kcal/d, with lower requirements, 1919 and 1699 kcal/d for the young-old (>or= 65 to < 75 y) and the old-old (>or= 75 y), respectively. Among females, the average energy requirements for the 3 age categories were 1712, 1662, and 1398 kcal/d, respectively. Actual energy intakes, however, were only approximately 65% adequate for all subjects as compared to energy expenditure. Protein, fat, and micronutrients (vitamins A and C, thiamin, riboflavin, iron and calcium) intakes were only approximately 24-51% of the recommended daily intake. Among this population, there was a weight decrease of 100 g (p = 0.012) and a BMI decrease of 0.04 kg/m2 (p = 0.003) for every 1% decrease in total caloric intake as percentage of the total energy expenditure requirements. CONCLUSION: These community living elderly suffer from lack of both macronutrient intake as compared with energy requirements, and micronutrient intake as compared with the standard dietary recommendations. Their energy intakes are ~65% of the amounts required based on their total energy expenditure. Though their intakes decrease with increasing age, so do their energy expenditure, making their relative insufficiency of food intake stable with age.

Efficacy of pandesal baked from wheat flour fortified with iron and vitamin a in improving the iron and anthropometric status of anemic schoolchildren in the Philippines.

OBJECTIVE: To determine the efficacy of pandesal baked from wheat flour fortified with iron, with or without vitamin A (VA), in improving anemic schoolchildren's iron and anthropometric status. METHODS: Anemic 6- to 12-year-old Filipino children (n = 250) received two 60 g pandesal daily for 8 months. They were randomized into 1 of 4 groups: (1) iron-fortified (with hydrogen-reduced iron at 80 mg/kg, electrolytic iron at 80 mg/kg, or ferrous fumarate at 40 mg/kg), (2) iron and VA-fortified, (3) VA-fortified (at 490 RE/100 g), and (4) nonfortified flour. Hemoglobin (Hb) and zinc protoporphyrin (ZnPP) concentrations and weight and height were determined before and after intervention. Analyses of variance and chi-square and multiple regression analyses were performed. RESULTS: Mean Hb increased by 1.3 g/dL (p < 0.001) and mean ZnPP decreased by 24.4 micromol/mol (p < 0.001) after 8 months. Anemia decreased to 26% and iron deficiency decreased from 58% to 12%. After controls were applied for baseline concentration, age, and gender, Hb concentration at post intervention was significantly higher in the Iron + VA group than in the nonfortified group (coefficient = 0.37; p = 0.034). The odds of being iron deficient at post intervention were significantly lower in the Iron group than in the nonfortified group after controls were applied for age, gender, and baseline prevalence (coefficient = 0.12; p = 0.006). None of the 3 fortified groups had significantly different weight-for-age z-score, body mass index-for-age z-score, or height-for-age z-score compared with the nonfortified group after controls were applied for baseline z-scores, age, and gender. CONCLUSIONS: Our study shows that in a non-malaria-endemic area, iron fortification of flour significantly reduced the prevalence of iron deficiency among anemic schoolchildren, and double fortification with iron and VA significantly improved Hb status.

Determinants of anemia among preschool children in the Philippines.

OBJECTIVE: Our objective was to identify the determinants of anemia among rural Filipino children aged 12-71 months. METHODS: A cross-sectional survey was conducted among 2090 preschool children from 8 rural villages in Cebu, an area non-endemic for malaria and schistosomiasis. Hemoglobin (Hb) concentration was determined using a HemoCue hemoglobinometer and zinc protoporphyrin (ZPP) concentration was measured with a hematofluorometer. A 3-day non-consecutive 24-hour food recall interview with the child's primary caregiver was done to estimate the child's dietary intake. Stool analysis for presence of soil-transmitted helminths was performed through a concentration technique. A separate interview on household socio-economic status with the child's primary caregiver was conducted. RESULTS: Mean Hb concentration was 12.0 g/dL (SD 1.3). 16.1% were anemic. Age and sex had a significant interaction in their effect on Hb concentration. Females had higher Hb concentration between 12 to 23 months of age. Hb levels equalize between the 2 genders at around 24 months and increase with similar increments until 71 months of age. All dietary parameters improved Hb concentration with increasing intake. In the multiple regression, however, only the index for bioavailable iron and vitamin C intakes remained independent factors. None of the helminths or combination of helminths had significant effects on Hb concentration. Among the socio-economic variables, maternal educational attainment and water supply were significant independent factors. Mean ZPP concentration was 72.07 (SD 46.45) and 30.8% were iron deficient. As with Hb concentration, age and sex had a significant interaction in their effect on ZPP concentration, with females having lower ZPP levels before 24 months of age. Bioavailable iron (animal iron + 0.3*plant iron) had a significant effect on ZPP concentration at levels of at least 15% of the iron requirement. This was seen even after controlling for multivitamin supplementation. CONCLUSION: The control of anemia among preschoolers can be achieved through a combination of various nutritional interventions such as micronutrient supplementation, food fortification and nutrition education. Our findings emphasize the importance of a multi-sectoral approach to nutritional problems--the importance of empowering women (through engagement and education) and of maintaining a healthy physical environment (water and sanitation) are often peripheral concerns of nutritionists. Our study highlights the importance of supporting initiatives that address these issues not only for their core benefit, but also for the potential benefit to nutrition.

Effectiveness of an early supplementation scheme of high-dose vitamin A versus standard WHO protocol in Gambian mothers and infants: a randomised controlled trial.

BACKGROUND: Most developing countries have adopted a standard WHO dosing schedule for vitamin A supplementation. However, in 2002 the International Vitamin A Consultative Group (IVACG) Annecy Accord recommended a new high-dose regimen for mothers and infants. Our aim was to test whether the new high-dose regimen of vitamin A supplementation would increase maternal and infant plasma vitamin A, reduce infant Helicobacter pylori infection and nasopharyngeal pneumococcal carriage, and improve infant gut epithelial integrity. METHODS: In an area of moderate vitamin A deficiency in rural Gambia, 220 mother-infant pairs were enrolled in a randomised double-blind trial between September, 2001, and October, 2004, that compared the IVACG high dose with the WHO dose. The primary endpoints were levels of maternal and infant plasma vitamin A, H pylori infection, pneumococcal carriage, and gut epithelial integrity. The trial is registered as ISRCTN 98554309. FINDINGS: 197 infants completed follow-up to 12 months (99 high dose and 98 WHO dose). There were no adverse events at dosing. No differences were found in the primary outcomes for high-dose versus WHO schedule: maternal vitamin A concentration at 2 months +0.02 micromol/L (95% CI -0.10 to 0.15); infant vitamin A at 5 months +0.01 micromol/L (-0.06 to 0.08); H pylori infection at 12 months -0.3% (-14.7 to 14.2); maternal pneumococcal carriage at 12 months -2.0% (-13.7 to 9.7); infant pneumococcal carriage at 12 months -4.1% (-15.8 to 7.6); infant gut mucosal damage at 12 months 5.2% (-8.7 to 19.2). There were more clinic attendances by the high-dose group in the first 6 months of life (p=0.018). INTERPRETATION: Our results do not lend support to the proposal to increase the existing WHO standard dosing schedule for vitamin A in areas of moderate vitamin A deficiency. Caution is urged for future studies because trials have shown possible adverse effects of higher doses of vitamin A, and potential negative interactions with the expanded programme on immunisation (EPI) vaccines.

Long-term effects of perinatal nutrition on T lymphocyte kinetics in young Gambian men.

BACKGROUND: Nutritional status is highly dependent on season in countries such as The Gambia. In a rural Gambian setting, individuals born during periods of seasonal nutritional deprivation ("hungry seasons") are susceptible to mortality from infectious diseases in adult life. OBJECTIVE: We investigated the hypothesis that impaired immunocompetence in those born in the hungry season results from an underlying defect in immunologic memory, similar to the immunosenescence of old age, which is likely to be reflected in the phenotype and kinetics of T lymphocytes in young adults. DESIGN: T cell phenotype in terms of CD3, CD4, CD8, CD45RA, and CD45R0 expression and in vivo dynamics measured by stable isotope labeling of T cell subsets combined with gas chromatography-mass spectrometry and frequency of T cell receptor excision circles were measured in 25 young (18-24-y-old) Gambian men. Thirteen of these 25 men were exposed to perinatal malnutrition as defined by birth season and birth weight. RESULTS: In persons born in the hungry season with low birth weight, no differences in the proportions of memory or naive T cells were found. Kinetic analysis showed higher proliferation rates in memory (CD45R0(+)) subsets of T cells than in naïve (CD45R0(-)) cells, which is consistent with previous studies, but no evidence was found for an effect of birth weight or season on T lymphocyte proliferation and disappearance rates. No significant correlations were found between in vivo T cell kinetics and frequency of T cell receptor excision circles. Only absolute numbers of granulocytes were elevated in those born in the nutritionally deprived season. CONCLUSION: In healthy young Gambian men, T lymphocyte homeostasis is extremely robust regardless of perinatal nutritional compromise.