Lynette Pei-Chi Shek

Epidemiology and seasonality of respiratory tract virus infections in the tropics

Acute viral respiratory tract infections are a significant cause of morbidity worldwide. Information on the epidemiology and seasonality of these infections is important in planning vaccination and treatment strategies. In temperate climes, there are distinct seasonal peaks in the winter months. This paper reviews the seasonal trends of respiratory viral infections in the tropics. Despite the absence of a winter season, consistent seasons of infection, albeit less distinct, have been observed. With few exceptions, respiratory syncytial virus and influenza infections have been observed mainly during the rainy seasons in Asian, African and South American countries.

International consensus on (ICON) anaphylaxis

ICON: Anaphylaxis provides a unique perspective on the principal evidence-based anaphylaxis guidelines developed and published independently from 2010 through 2014 by four allergy/immunology organizations. These guidelines concur with regard to the clinical features that indicate a likely diagnosis of anaphylaxis -- a life-threatening generalized or systemic allergic or hypersensitivity reaction.They also concur about prompt initial treatment with intramuscular injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the patient supine (semi-reclining if dyspneic or vomiting), calling for help, and when indicated, providing supplemental oxygen, intravenous fluid resuscitation and cardiopulmonary resuscitation, along with concomitant monitoring of vital signs and oxygenation. Additionally, they concur that H1-antihistamines, H2-antihistamines, and glucocorticoids are not initial medications of choice.For self-management of patients at risk of anaphylaxis in community settings, they recommend carrying epinephrine auto-injectors and personalized emergency action plans, as well as follow-up with a physician (ideally an allergy/immunology specialist) to help prevent anaphylaxis recurrences.ICON: Anaphylaxis describes unmet needs in anaphylaxis, noting that although epinephrine in 1 mg/mL ampules is available worldwide, other essentials, including supplemental oxygen, intravenous fluid resuscitation, and epinephrine auto-injectors are not universally available.ICON: Anaphylaxis proposes a comprehensive international research agenda that calls for additional prospective studies of anaphylaxis epidemiology, patient risk factors and co-factors, triggers, clinical criteria for diagnosis, randomized controlled trials of therapeutic interventions, and measures to prevent anaphylaxis recurrences. It also calls for facilitation of global collaborations in anaphylaxis research.In addition to confirming the alignment of major anaphylaxis guidelines, ICON: Anaphylaxis adds value by including summary tables and citing 130 key references. It is published as an information resource about anaphylaxis for worldwide use by healthcare professionals, academics, policy-makers, patients, caregivers, and the public.

The prevalence of asthma and allergies in Singapore; data from two ISAAC surveys seven years apart

Background and Aims: Over the past few decades, the prevalence of asthma has been increasing in the industrialised world. Despite the suggestion of a similar increase in Singapore, the 12 month prevalence of wheeze among schoolchildren in 1994 was 2.5-fold less than that reported in western populations. It was hypothesised that with increasing affluence in Singapore, the asthma prevalence would further increase and approach Western figures. A second ISAAC survey was carried out seven years later to evaluate this hypothesis. Methods: The cross-sectional data from two ISAAC questionnaire based surveys conducted in 1994 (n = 6238) and in 2001 (n = 9363) on two groups of schoolchildren aged 6–7 and 12–15 years were compared. The instruments used were identical and the procedures standardised in both surveys. Results: Comparing data from both studies, the change in the prevalence of current wheeze occurred in opposing directions in both age groups—decreasing in the 6–7 year age group (16.6% to 10.2%) but increasing to a small extent in the 12–15 year age group (9.9% to 11.9%). The 12 month prevalence of rhinitis did not change; there was an increase in the current eczema symptoms in both age groups. Conclusion: The prevalence of current wheeze, a surrogate measure of asthma prevalence, has decreased significantly in the 6–7 year age group. Eczema was the only allergic disease that showed a modest increase in prevalence in both age groups.

Distinct pattern of commensal gut microbiota in toddlers with eczema.

Background: Recent studies have demonstrated differences in the composition of gut microbiota in infants with and without allergic diseases, particularly eczema. Methods: A case-control study involving 21 toddlers (age 3.0 ± 0.5 years) with and 28 age-matched toddlers without eczema was conducted. Four groups of aerobic gut microbiota were identified and quantitated in stool samples grown on selective media. Three groups of anaerobes were enumerated by fluorescent in situ hybridization followed by quantitative flow cytometry. We also performed molecular typing of lactic-acid-producing bacteria (LAB) and enterococcal isolates to facilitate detailed analysis at species level by bacterial 16S rDNA sequencing. Results: Toddlers with eczema harbored significantly lower counts of Bifidobacterium [(median 0.14 (25th and 75th percentile: 0.04 and 0.47) vs. 0.71% (0.16, 1.79) of cells acquired, p = 0.003)] and Clostridium [(0.28 (0.09, 0.78) vs. 0.83% (0.35, 1.82) of cells acquired, p = 0.012)] but significantly higher counts of total LAB [7.3 (6.1, 8.5) vs. 5.7 (4.4, 7.3) log CFU/g, p = 0.006] in particular enterococci [6.3 (4.8, 7.4) vs. 5.0 (3.4, 6.4) log CFU/g, p = 0.018]. There was no significant correlation between eczema severity score and bifidobacterial counts. Conclusion: The results further confirm previous reports that the gut microecosystem differs between children with and without eczema and extend them beyond infancy.

PATTERN OF FOOD-INDUCED ANAPHYLAXIS IN CHILDREN OF AN ASIAN COMMUNITY

a tricyclic antidepressant. In week 4 of the treatment with phenytoin, the patient developed in 24±48 h fever of 398C combined with generalized erythematous skin rash. The other systemic and neurologic probes were normal. The blood cell count showed leukocytosis with eosinophilia (16 500 leukocytes/mm, 12% eosinophils), and the coagulation study, biochemical and hepatic pro®le, hemocultures, coprocultures, and urocultures then done, as well as the chest radiography, were normal. Computed tomography of the skull described the continuity to a parietal level without any other important alteration. With the clinical suspicion that there was an adverse reaction to medication, the phenytoin and the tricyclic antidepressant were stopped. During the following week, the patient continued to show fever and eosinophilia, and the skin rash became desquamative. The clinical situation worsened gradually and between days 8 and 10 after stopping the phenytoin, she showed acute hepatic failure with high cytolysis and cholestasis (glucose 57 mg/dl, SGOT 1535 U/l, SGPT 497 U/l, gamma GT 1055 U/l, alkaline phosphatase 662 U/l, cholesterol 110 mg/dl, total bilirubin 17.5 mg/dl, LDH 2862 U/l, albumin 1.7 g/dl), linked to severe coagulopathy (prothrombin Ac. 21%, APTT 53/29). The analysis then done did not reveal any indication of a possible cause, and the abdominal echography showed only a spleen slightly increased in size. In the following days, the patient developed acute renal failure and pancytopenia with severe neutropenia (2400 leukocytes/mm with 190 neutrophils, 10 000 blood platelets/mm, hemoglobin 8.9 g/dl). The patient died 15 days after stopping the phenytoin. The autopsy showed submassive hepatic necrosis linked to splenomegaly, and moderate in ̄ammatory in®ltrated vascular congestion of the skin. The anatomopathologic diagnosis was phenytoin hypersensitivity syndrome. Phenytoin is an anticonvulsant affecting hepatic metabolism. Among its more frequent side-effects are gastric intolerance, skin rash, and gingival hyperplasia. Less frequently, cases of hypersensitivity syndrome to DFH have been described. This syndrome with anticonvulsants was ®rst described in 1950 by Chaiken et al. (1); they called it dilantin hypersensitivity syndrome. Later, cases involving carbamacepine, primidone, and phenobarbital were described. The hypersensitivity syndrome to phenytoin is of low incidence (1/1000±10 000 treated with DFH), and it usually appears between weeks 1 and 4 of treatment. Risk factors have not been clearly identi®ed when they appeared and their origin is not dose dependent. Skin signs were the most common in the syndrome in the study by Silverman (2). Fever, lymphadenopathies, and megalies are common, as well as leukocytosis and eosinophilia. Aplastic marrow and hepatic affectation are less common. Those rare signs appear late during the development of the syndrome, and most of the patients who develop them have previous skin alterations. The pathogenic mechanism of this syndrome has not been established. Most of the facts suggest a hypersensitivity phenomenon, although idiosyncratic and toxic mechanisms with enzymatic induction of Cp 450 and the production of intermediary metabolites have also been involved. These metabolites are potentially cytotoxic, and they can alter the lymphocytic function, increasing the hepatocellular necrosis and lymphadenopathies, as described by Haword et al. (3). The diagnosis of this syndrome is clinical and analytic. Studies of lymphocytic stimulation and the patch test can indicate the therapeutic option of withdrawal of DFH, although the patients condition can alter. This emphasizes the danger of a premature diagnosis. Steroids are usually used during the treatment, although their indexing is not well established and does not alter the mortality rate. However, they are effective in the skin symptoms and can shorten their course. Excessive medication taken with DFH can worsen the prognosis. Dreifuss et al. (4) have shown cross-reactivity with other anticonvulsants and interaction with antidepressants. The mortality rate in this syndrome rises to 30±40% if hepatic damage occurs. Mullick (5), in a clinical pathologic study, has reported 20 cases of hepatic injury associated with diphenylhydantoin; the mortality rate without hepatic affectation was 10%. Our patient showed hypersensitivity syndrome to DFH after 4 weeks of treatment. She developed fever, desquamative erythema, and eosinophilia linked to aplastic marrow and severe hepatic failure, which caused her death.

Immunogenicity and safety of recombinant tetravalent dengue vaccine (CYD-TDV) in individuals aged 2-45 years Phase II randomized controlled trial in Singapore

This was a multicenter, blinded, Phase II study (NCT00880893) conducted in Singapore. The primary objectives were to evaluate the safety of a tetravalent dengue vaccine (TDV) comprising four recombinant, live, attenuated viruses (CYD-TDV) and the dengue virus serotype-specific antibody responses before and 28 d after each vaccination. Participants were randomized 3:1 to receive three doses of CYD-TDV or a control vaccine at 0, 6 and 12 mo. Control vaccine was placebo for the first dose (all ages) and for subsequent doses, licensed hepatitis-A for children (aged 2–11 years) or influenza vaccine for adolescents (12–17 years) and adults (18–45 years). Between April and October 2009, 317 children, 187 adolescents and 696 adults were enrolled. In all age groups, reactogenicity was higher after the first injection of CYD-TDV than after placebo control. Reactogenicity after subsequent CYD-TDV doses was no higher than after the first dose, and tended to be lower or similar to that seen after active control vaccination. Seropositivity rates and geometric mean neutralizing antibody titers (GMTs; 1/dil) against all four dengue virus serotypes increased in all age groups after each of the three CYD-TDV doses. Post-dose 3, 66.5% of all participants were seropositive to all four serotypes, and 87.2% were seropositive to ≥ 3 serotypes; GMTs for all participants ranged from 43.0 against dengue virus serotype 1 to 100 against dengue virus serotype 4. GMTs were higher in children than in adolescents. These results support the continued development of CYD-TDV for the prevention of dengue disease.This was a multicenter, blinded, Phase II study (NCT00880893) conducted in Singapore. The primary objectives were to evaluate the safety of a tetravalent dengue vaccine (TDV) comprising four recombinant, live, attenuated viruses (CYD-TDV) and the dengue virus serotype-specific antibody responses before and 28 d after each vaccination. Participants were randomized 3:1 to receive three doses of CYD-TDV or a control vaccine at 0, 6 and 12 mo. Control vaccine was placebo for the first dose (all ages) and for subsequent doses, licensed hepatitis-A for children (aged 2-11 y) or influenza vaccine for adolescents (12-17 y) and adults (18-45 y). Between April and October 2009, 317 children, 187 adolescents and 696 adults were enrolled. In all age groups, reactogenicity was higher after the first injection of CYD-TDV than after placebo control. Reactogenicity after subsequent CYD-TDV doses was no higher than after the first dose, and tended to be lower or similar to that seen after active control vaccination. Seropositivity rates and geometric mean neutralizing antibody titers (GMTs; 1/dil) against all four dengue virus serotypes increased in all age groups after each of the three CYD-TDV doses. Post-dose 3, 66.5% of all participants were seropositive to all four serotypes, and 87.2% were seropositive to ≥ 3 serotypes; GMTs for all participants ranged from 43.0 against dengue virus serotype 1 to 100 against dengue virus serotype 4. GMTs were higher in children than in adolescents. These results support the continued development of CYD-TDV for the prevention of dengue disease.

Parvalbumin : the major tropical fish allergen

Fish allergy is common in countries where consumption is high. Asian nations are amongst the world’s largest consumers of fish but the allergen profiles of tropical fish are unknown. This study sought to evaluate the allergenicity of four commonly consumed tropical fish, the threadfin (Polynemus indicus), Indian anchovy (Stolephorus indicus), pomfret (Pampus chinensis) and tengirri (Scomberomorus guttatus). Immunoglobulin E (IgE) cross‐reactivity with parvalbumin of cod fish (Gad c 1), the major fish allergen, was also studied. Detection of tropical fish and cod specific‐IgE was performed by UniCap assay, and skin prick tests were also carried out. The IgE‐binding components of tropical fish were identified using IgE immunoblot techniques, and cross‐reactivity with Gad c 1 was assessed by ELISA inhibition and IgE immunoblot inhibition. Clinically, nine of 10 patients studied were allergic to multiple fish. All patients exhibited detectable specific‐IgE to cod fish (10 of 10 skin prick test positive, eight of 10 UniCap assay positive) despite lack of previous exposure. The major allergen of the four tropical fish was the 12‐kDa parvalbumin. IgE cross‐reactivity of these allergens to Gad c 1 was observed to be moderate to high in the tropical fish studied. Parvalbumins are the major allergens in commonly consumed tropical fish. They are cross‐reactive with each other as well as with Gad c 1. Commercial tests for cod fish appear to be sufficient for the detection of tropical fish specific‐IgE.

Food allergy in Asia

Purpose of review Food allergy is increasing in prevalence in Western populations, but little is known about it in Asia. The perception is that the prevalence in this region is low, but is likely to increase with the global increase in allergy. Asia is unique because of the many different cultures and eating habits, with the resulting occurrence of unique food allergens. This review describes the epidemiology and clinical features of food allergy, and introduces some of the unusual food allergens in Asia. Recent findings Recent studies describing the pattern of anaphylaxis and the role of food triggers show that food is an important cause of severe allergic reactions in Asia. Progress has been made on the characterization of unique food allergens from the region. Peanut and tree nuts are rarely the cause of allergic reactions in Asia. The lack of availability of epinephrine auto-injectors in many countries is an important issue that needs to be addressed. Summary The pattern of food allergy in Asia is unique. Unfortunately, data from many parts of Asia are still lacking. Large, well-designed epidemiological studies are needed so that the scale of the problem can be understood, public awareness can be increased and important food allergens in the region can be identified.

Use of hypoallergenic formula in the prevention of atopic disease among Asian children.

Objective: To determine the effect of a partially hydrolysed formula on genetically predisposed children, with respect to the development of atopic clinical manifestations and in vitro testing of serum IgE levels (total and milk‐specific).

Effect of a Milk Formula Containing Probiotics on the Fecal Microbiota of Asian Infants at Risk of Atopic Diseases

The fecal microbiota of 37 infants with (n = 20) or without (n = 17) probiotic administration was evaluated on D 3, and at 1, 3, and 12 mo by fluorescence in situ hybridization-flow cytometry (FISH-FC), PCR, and bacteriological culture methods. They represent consecutive subjects of an ongoing double-blind, placebo-controlled trial on a probiotic formula (LGG and Bifidobacterium longum) administered during the first 6 mo of life. Despite varying composition in each baby, there was a general bacterial colonization pattern in the first year. Bifidobacteria increased markedly (p = 0.0003) with a parallel decrease in Enterobacteriaceae (p < 0.001) and Bacteroides–Prevotella (p = 0.005) populations. Eubacterium rectale–Clostridium coccoides (p < 0.001) and Atopobium (p = 0.039) groups also gradually increased. This overall pattern was unaffected by probiotic administration (p > 0.05). B. longum (p = 0.005) and Lactobacillus rhamnosus (p < 0.001) were detected more frequently in probiotic group during supplementation, but no difference after supplementation had ceased (p > 0.05). Cultured lactic acid bacteria were also more numerous in the probiotic-administered babies during treatment period (log10 CFU/g 8.4 versus 7.4; p = 0.035). Our results indicate that supplemented strains could be detected but did not persist in the bowel once probiotic administration had ceased.