Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes. For some patients, dengue is a life-threatening illness. There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread. The contemporary worldwide distribution of the risk of dengue virus infection and its public health burden are poorly known. Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of disease severity). This infection total is more than three times the dengue burden estimate of the World Health Organization. Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation.

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The global distribution and burden of dengue

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

https://gut.bmj.com/content/gutjnl/66/1/6.full.pdf

Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report

Management of Helicobacter pylori infection is evolving and in this 4th edition of the Maastricht consensus report aspects related to the clinical role of H pylori were looked at again in 2010. In the 4th Maastricht/Florence Consensus Conference 44 experts from 24 countries took active part and examined key clinical aspects in three subdivided workshops: (1) Indications and contraindications for diagnosis and treatment, focusing on dyspepsia, non-steroidal anti-inflammatory drugs or aspirin use, gastro-oesophageal reflux disease and extraintestinal manifestations of the infection. (2) Diagnostic tests and treatment of infection. (3) Prevention of gastric cancer and other complications. The results of the individual workshops were submitted to a final consensus voting to all participants. Recommendations are provided on the basis of the best current evidence and plausibility to guide doctors involved in the management of this infection associated with various clinical conditions.

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Management of Helicobacter pylori infection—the Maastricht IV/ Florence Consensus Report

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)61693-6.pdf

What works? Interventions for maternal and child undernutrition and survival.

OBJECTIVE: To review the evidence about the prevalence and determinants of non-psychotic common perinatal mental disorders (CPMDs) in World Bank categorized low- and lower-middle-income countries. METHODS: Major databases were searched systematically for English-language publications on the prevalence of non-psychotic CPMDs and on their risk factors and determinants. All study designs were included. FINDINGS: Thirteen papers covering 17 low- and lower-middle-income countries provided findings for pregnant women, and 34, for women who had just given birth. Data on disorders in the antenatal period were available for 9 (8%) countries, and on disorders in the postnatal period, for 17 (15%). Weighted mean prevalence was 15.6% (95% confidence interval, CI: 15.4-15.9) antenatally and 19.8% (19.5-20.0) postnatally. Risk factors were: socioeconomic disadvantage (odds ratio [OR] range: 2.1-13.2); unintended pregnancy (1.6-8.8); being younger (2.1-5.4); being unmarried (3.4-5.8); lacking intimate partner empathy and support (2.0-9.4); having hostile in-laws (2.1-4.4); experiencing intimate partner violence (2.11-6.75); having insufficient emotional and practical support (2.8-6.1); in some settings, giving birth to a female (1.8-2.6), and having a history of mental health problems (5.1-5.6). Protective factors were: having more education (relative risk: 0.5; P = 0.03); having a permanent job (OR: 0.64; 95% CI: 0.4-1.0); being of the ethnic majority (OR: 0.2; 95% CI: 0.1-0.8) and having a kind, trustworthy intimate partner (OR: 0.52; 95% CI: 0.3-0.9). CONCLUSION: CPMDs are more prevalent in low- and lower-middle-income countries, particularly among poorer women with gender-based risks or a psychiatric history.

/pdf/prevalence-and-determinants-of-common-perinatal-mental-3vicnewjrh.pdf

Prevalence and determinants of common perinatal mental disorders in women in low- and lower-middle-income countries: a systematic review

Introduction Vitamin B12 deficiency is widely prevalent across many low- and middle-income countries, especially where the diet is low in animal sources. While many observational studies show associations between B12 deficiency in pregnancy and infant cognitive function (including memory, language and motor skills), evidence from clinical trials is sparse and inconclusive. Methods and analysis This double-blind, multicentre, randomised controlled trial will enrol 720 vegetarian pregnant women in their first trimester from antenatal clinics at two hospitals (one in India and one in Nepal). Eligible mothers who give written consent will be randomised to receive either 250 mcg methylcobalamin or 50 mcg (quasi control), from enrolment to 6 months post-partum, given as an oral daily capsule. All mothers and their infants will continue to receive standard clinical care. The primary trial outcome is the offspring’s neurodevelopment status at 9 months of age, assessed using the Development Assessment Scale of Indian Infants. Secondary outcomes include the infant’s biochemical B12 status at age 9 months and maternal biochemical B12 status in the first and third trimesters. Maternal biochemical B12 status will also be assessed in the first trimester. Modification of association by a priori identified factors will also be explored. Ethical considerations and dissemination The study protocol has been approved by ethical committees at each study site (India and Nepal) and at University College London, UK. The study results will be disseminated to healthcare professionals and academics globally via conferences, presentations and publications. Researchers at each study site will share results with participants during their follow-up visits. Trial registration number CTRI/2018/07/015048 (Clinical Trial Registry of India); NCT04083560 (ClinicalTrials.gov)

https://bmjopen.bmj.com/content/bmjopen/10/5/e034987.full.pdf

Efficacy of maternal B12 supplementation in vegetarian women for improving infant neurodevelopment: protocol for the MATCOBIND multicentre, double-blind, randomised controlled trial.

To The Editor: Helicobacter pylori is a Gram negative, spiral-shaped bacterium found in the gastric mucous layer which is now implicated in peptic ulcer disease, chronic gastritis, gastric adenocarcinoma and mucosa associated lymphoid tissue lymphoma, and duodenal ulcer disease. Eradication of H. pylori is considered a necessary step in the management of these diseases. Standard triple therapy eradication regimens (proton pump inhibitor plus clarithromycin and amoxicillin or nitroimidazole) achieve unpredictable and often poor results. The second line quadruple regimens are further limited by poorer patient compliance and increased side effects. In this context, several alternative and complimentary therapies have been tried in an attempt to achieve better eradication without affecting compliance. In this search, fermented milk and several of its component, whey proteins, have emerged as potential candidates for complementary therapy. We reviewed the current evidence. Fermented milk refers to whole or skimmed milk curdled to a beverage or custard like consistency by lactic acid producing bacteria. A wide assortment of products varying by the process, bacteria, duration, and other variables are available and widely consumed in different countries. However, there are several commonalities. Fermented milk possesses a protein system constituted by 2 major families of proteins that is, casein and whey proteins. Casein is insoluble, account for 80% of protein inventory. Whey proteins are water soluble and include bovine lactoferrin (bLf), a-lactalbumin (a-LA), glycomacropeptide (GMP), immunoglobulin (IG), b-lactoglobulin, and lactoperoxidase. In the context of the H. pylori eradication, there is a fair body of evidence from trials conducted using fermented milk or fermented milkbased probiotic preparations (FMPPs). A recent systematic review of randomized controlled trials compared an FMPP versus placebo or standard therapy plus FMPP versus standard therapy and documented a beneficial effect of FMPPs. The overall quality and quantity of evidence for FMPPs seems convincing and beneficial effect seems to be sustained when FMPPs were used in combination with standard therapy. Also, the benefit seems to be similar in symptomatic children, symptomatic and asymptomatic adults, and in patients with failed eradication on standard therapy and holds across a variety of preparations. FMPPs also carry the potential inherent advantage of better patient acceptability. In this light they could offer a viable alternative for complementing traditional regimens. However, the magnitude of documented benefit is small (5% to 15%). Further research is necessary to identify the active substrate/s and to define the exact product to be used, the optimal clinical setting (prevention/treatment, first line therapy/recurrence, symptomatic/asymptomatic, gastritis/ulcer diseases, treatment failure etc.) and potential benefits in the setting of high antibiotic resistance. Whey proteins are globular water soluble molecules constituting B20% of the milk protein system. Beta-lactoglobulin comprises the maximum percentage of whey protein but it has not been documented to possess any antibacterial properties. The bLf, an iron-binding glycoprotein, is a nonenzymatic antioxidant found in the whey fraction of fermented milk and in colostrum. The possibility that bLF may help to improve the H. pylori eradication rate was first conceived in 1997 when, in an in vitro study by Yamazaki et al bLf was found to be bactericidal to H. pylori in brucella broth. The experimental evidence led to several human clinical trials. Five of seven available clinical trials and a meta-analysis of randomized controlled trails support the beneficial effect of bLf (4% to 17% improvement in eradication rate as per metaanalysis) on H. pylori eradication. Two studies by Zullo et al did not show any significant difference on addition of lactoferrin to triple therapy. Although the available evidence suggests that bLf is beneficial, the magnitude of the documented benefit is small. Given that it lacks the inherent advantage in patient acceptability (requires to be given as a drug) that fermented milk potentially has, the clinical significance of the benefit (other than suggesting that whey protein may be partly/completely responsible for the benefit with FMPP) remains unclear. Its role in various clinical settings and more so in the presence of high antibiotic resistance deserves further exploration. Alpha-LA is a major milk protein comprising 20% to 25% of whey proteins and has strong calcium binding ability. Alpha-LA is reported to be biologically active in vivo with well demonstrated antiulcer activity in rats. Matsumoto et al in an in vivo study using ethanol, ulcer model rats documented 82% reduction of ulcerative lesion index using 200mg/kg body weight of a-LA. Similar results were reported by Mezzaroba et al, with absolute alcohol and indomethacin, ulcer model rats given commercial a-LA. This intervention resulted in 30% to 70% lower ulcerative lesion index in comparison with controls. The exact mechanism of the protective effect and its impact on Helicobacter is not well studied, although as reported whey protein concentrates have consistently reported anti-helicobacter properties. The scarcity of evidence on the subject precludes any definitive comment on the potential of a-LA as an anti-helicobacter agent. However, the paucity of literature on the subject presents wide scope for future research. GMP also referred to as caseinomacropeptide and caseinoglycopeptide, is formed when bovine k-casein is hydrolyzed into para-k-casein which remains with the curd and GMP is removed with the whey. It constitutes 15% to 20% of whey protein. GMP has also been found to have several immunomodulatory functions and antibacterial properties. Otani et al demonstrated that GMP which contains sialic acid inhibits the activity of Salmonella typhimurium lipopolysaccharide, inhibiting bacterial and viral adhesion especially to epithelial cells. A study done in Japan attempted to enhance the ability of glycopeptides to bind pathogenic bacteria in vivo by conjugating with the nondigestible Conflict of interest: None to declare. Supported by intramural funding by Sitaram Bhartia Institute of Science and Research, New Delhi. LETTERS TO THE EDITOR

Emerging health properties of fermented milk and whey proteins: Role in Helicobacter pylori eradication.

Authors' reply re: Widespread non-adherence to evidencebased maternity care guidelines: a population-based cluster randomised household survey

http://www.aimdrjournal.com/pdf/vol4Issue1/PY1_OA_V4N1.pdf

To Compare Perceived Stress In Shift Duty Health Professionals

<h3>Objectives</h3> Vitamin B-12 deficiency is common in many low- and low-middle-income countries. Vegetarian dietary practices often contribute to this high prevalence. Several observational studies have documented the association of B-12 deficiency in pregnancy with poor neurodevelopment amongst infants [1,2]. However, clinical trials are few and inconclusive [3,4]. Hence, the current clinical trial proposed to evaluate the efficacy of maternal B-12 supplementation in vegetarian pregnant women for improving- Infant neurodevelopment at 9 months of age Biochemical B-12 status in mothers at the end of 3rd trimester and in infants at 9 months <h3>Methods</h3> This multi-center, double-blind, randomized controlled trial enrolled 708 vegetarian women in their first trimester from tertiary care facilities in New Delhi, India (n=370) and Kathmandu, Nepal (n=338). Mothers were randomized to receive oral methyl-cobalamin supplementation (250 mcg (Group-A) or 50 mcg (Group-B; quasi-control)) from enrollment to 6-months postpartum as daily capsules. Anthropometry, interval/current morbidity, medical advice (medicines/supplements), and dietary intake were recorded at the facility visits of the mother and infant through pregnancy, childbirth, and infancy. Infant neurodevelopment at 9 months was assessed using the Development Assessment Scale of Indian Infants[5] and the home environment was evaluated using the Bradley HOME inventory[6]. Change in maternal B-12 status between enrollment and the 3rd trimester, and infant B-12 status at 9 months of age were estimated. <h3>Results</h3> 531 subjects completed the study (177 lost to follow-up; comparable for baseline characteristics). The two groups were similar for baseline characteristics (Group-A n=255; Group-B n=276; p&gt;0.05). Table 1 summarizes the outcomes. As presented mean increase in maternal B-12 levels between 1st and 3rd trimester was greater in Group-A (mean, SD): 104.9[159.1] than Group-B 47.5[118.0] pg/ml; p&lt;0.01. Similar improvements were noted in Holo-TC levels (p&lt;0.01) while the changes in Serum Ferritin, Vitamin-D and Folate were similar between the two groups (p&gt;0.05) as expected. Newborn anthropometry, morbidity profiles and APGAR Scores were similar between the two groups (p&gt;0.05). Milk feeding, complementary feeding, interval morbidity, growth and HOME scores were also comparable between the two groups (p&gt;0.05). Mental Developmental Quotient(DQ) was higher in Group-A: 103.7[7.7] vs. Group-B: 101.7[8.8]; p&lt;0.01) corresponding to a mean difference of 7.8 centiles (p&lt;0.01). Mean Motor DQ, infant B-12 status and newborn and infant anthropometry were similar between the two groups (p&gt;0.05). <h3>Conclusion</h3> Maternal B-12 status improvement and Mental DQ at 9 months are statistically significantly better with 250 mcg/d B-12 supplementation of vegetarian pregnant women compared with 50 mcg/d. <h3>References</h3> Dror DK, Allen LH. Effect of vitamin B12 deficiency on neurodevelopment in infants: Current knowledge and possible mechanisms Vol. 66, <i>Nutrition Reviews</i>. 2008:250–5. Sklar R. Nutritional vitamin B12 deficiency in a breast-fed infant of a vegan-diet mother. <i>Clin Pediatr (Phila)</i> 1986;<b>25</b>(4):219–21. Srinivasan K, Thomas T, Kapanee ARM, Ramthal A, Bellinger DC, Bosch RJ, <i>et al</i>. Effects of maternal vitamin B12 supplementation on early infant neurocognitive outcomes: a randomized controlled clinical trial. <i>Matern Child Nutr.</i> 2016;doi: 10.1111/mcn.12325. Siddiqua TJ, Ahmad SM, Ahsan KB, Rashid M, Roy A, Rahman SM, <i>et al</i>. Vitamin B12 supplementation during pregnancy and postpartum improves B12 status of both mothers and infants but vaccine response in mothers only: a randomized clinical trial in Bangladesh. <i>Eur J Nutr.</i> 2016 Feb;<b>55</b>(1):281–93. Patni B. Developmental Assessment Scales for Indian Infants (DASII). <i>Indian J Pract Pediatr.</i> 2012 [cited 2017 Apr 9];<b>14</b>(4):409–12. Bradley RH, Caldwell BM, Rock SL, Ramey CT, Barnard KE, Gray C, <i>et al</i>. Home environment and cognitive development in the first 3 years of life: a collaborative study involving six sites and three ethnic groups in NorthAmerica. <i>Developmental Psychology</i> 1989;<b>25</b>(2):217. 

327 Maternal B-12 supplementation in vegetarian pregnant women improves maternal B-12 status and infant neurodevelopment: The MATCOBIND multi-centric double-blind randomised-control-trial

Jitender Nagpal

Papers

Efficacy of maternal B12 supplementation in vegetarian women for improving infant neurodevelopment: protocol for the MATCOBIND multicentre, double-blind, randomised controlled trial.

Emerging health properties of fermented milk and whey proteins: Role in Helicobacter pylori eradication.

Authors' reply re: Widespread non-adherence to evidencebased maternity care guidelines: a population-based cluster randomised household survey

To Compare Perceived Stress In Shift Duty Health Professionals

327 Maternal B-12 supplementation in vegetarian pregnant women improves maternal B-12 status and infant neurodevelopment: The MATCOBIND multi-centric double-blind randomised-control-trial