Outcomes among children and adults at risk of severe dengue in Sri Lanka: Opportunity for outpatient case management in countries with high disease burden

BackgroundHealthcare systems in dengue-endemic countries are often overburdened due to the high number of patients hospitalized according to dengue management guidelines. We systematically evaluated clinical outcomes in a large cohort of patients hospitalized with acute dengue to support triaging of patients to ambulatory versus inpatient management in the future.Methods/Principal findingsFrom June 2017- December 2018, we conducted surveillance among children and adults with fever within the prior 7 days who were hospitalized at the largest tertiary-care (1,800 bed) hospital in the Southern Province, Sri Lanka. Patients who developed platelet count ≤100,000/μL (threshold for hospital admission in Sri Lanka) and who met at least two clinical criteria consistent with dengue were eligible for enrollment. We confirmed acute dengue by testing sera collected at enrollment for dengue NS1 antigen or IgM antibodies. We defined primary outcomes as per the 1997 and 2009 World Health Organization (WHO) classification criteria: dengue hemorrhagic fever (DHF; WHO 1997), dengue shock syndrome (DSS; WHO 1997), and severe dengue (WHO 2009). Overall, 1064 patients were confirmed as having acute dengue: 318 (17.4%) by NS1 rapid antigen testing and 746 (40.7%) by IgM antibody testing. Of these 1064 patients, 994 (93.4%) were adults ≥18 years and 704 (66.2%) were male. The majority (56, 80%) of children and more than half of adults (544, 54.7%) developed DHF during hospitalization, while 6 (8.6%) children and 22 (2.2%) adults developed DSS. Overall, 10 (14.3%) children and 113 (11.4%) adults developed severe dengue. A total of 2 (0.2%) patients died during hospitalization.ConclusionsOne-half of patients hospitalized with acute dengue progressed to develop DHF and a very small number developed DSS or severe dengue. Developing an algorithm for triaging patients to ambulatory versus inpatient management should be the future goal to optimize utilization of healthcare resources in dengue-endemic countries.     

Spatiotemporal distribution of cutaneous leishmaniasis in Sri Lanka and future case burden estimates

BackgroundLeishmaniasis is a neglected tropical vector-borne disease, which is on the rise in Sri Lanka. Spatiotemporal and risk factor analyses are useful for understanding transmission dynamics, spatial clustering and predicting future disease distribution and trends to facilitate effective infection control.MethodsThe nationwide clinically confirmed cutaneous leishmaniasis and climatic data were collected from 2001 to 2019. Hierarchical clustering and spatiotemporal cross-correlation analysis were used to measure the region-wide and local (between neighboring districts) synchrony of transmission. A mixed spatiotemporal regression-autoregression model was built to study the effects of climatic, neighboring-district dispersal, and infection carryover variables on leishmaniasis dynamics and spatial distribution. Same model without climatic variables was used to predict the future distribution and trends of leishmaniasis cases in Sri Lanka.ResultsA total of 19,361 clinically confirmed leishmaniasis cases have been reported in Sri Lanka from 2001–2019. There were three phases identified: low-transmission phase (2001–2010), parasite population buildup phase (2011–2017), and outbreak phase (2018–2019). Spatially, the districts were divided into three groups based on similarity in temporal dynamics. The global mean correlation among district incidence dynamics was 0.30 (95% CI 0.25–0.35), and the localized mean correlation between neighboring districts was 0.58 (95% CI 0.42–0.73). Risk analysis for the seven districts with the highest incidence rates indicated that precipitation, neighboring-district effect, and infection carryover effect exhibited significant correlation with district-level incidence dynamics. Model-predicted incidence dynamics and case distribution matched well with observed results, except for the outbreak in 2018. The model-predicted 2020 case number is about 5,400 cases, with intensified transmission and expansion of high-transmission area. The predicted case number will be 9115 in 2022 and 19212 in 2025.ConclusionsThe drastic upsurge in leishmaniasis cases in Sri Lanka in the last few year was unprecedented and it was strongly linked to precipitation, high burden of localized infections and inter-district dispersal. Targeted interventions are urgently needed to arrest an uncontrollable disease spread.     

Prevalence and resting behaviour of dengue vectors,Aedes aegypti and Aedes albopictus in dengue high risk urban settings in Colombo,Sri Lanka

Understanding local geographical variation in vector density and bionomics related to virus transmission are critical for planning effective vector control programs to control dengue virus transmission. This study investigated the prevalence and resting behaviour of Aedes aegypti and Ae. albopictus in three dengue high-risk areas in the Colombo District, Sri Lanka. Monthly sampling of resting adult mosquitoes was conducted from August 2019 to February 2020. Thirty-seven percent of the households (289/776) harboured Aedes mosquitoes, and 603 Aedes mosquitoes were collected. The proportion of Ae. aegypti was higher in the overall collection during the collection period (94% [569/603]), and 62% (352/569) were females. Significant monthly variations in Ae. aegypti were observed with respect to the indices: number of females per surveyed house (F/SH; p = 0.001), number of females per Aedes positive house (F/PH; p = 0.029), adult house index (AHI; p = 0.001), adult density (AD; p = 0.005) and resting ratio (RR; p = 0.001). AHI, AD, and RR had statistically significant positive correlations with monthly rainfall (p = 0.001, p = 0.011, and p = 0.002 respectively) and one-month lagged dengue cases (p = 0.002, p = 0.005, and p < 0.001 respectively). A statistically significantly higher proportion of Ae. aegypti females were caught resting indoors (N = 309, 88%) than outdoors (N = 43, 12%; p < 0.001). The most common resting areas were bedrooms (51%) & living/dining rooms (37%), and places were under or on furniture (47%) & hangings (34%) for Ae. aegypti. Conversely, 74% of female Ae. albopictus were collected outdoors. Results of this study could have strong implications to improve vector surveillance and control by early detection of dengue to detect outbreaks and minimization of disease transmission.     

Movement among healers in Sri Lanka: A case study of a sinhalese patient

Sinhalese patients in Sri Lanka have a variety of practitioners to choose from in seeking treatment for illness. These include: Ayurvedic physicians, Western physicians, and ritual practitioners. This paper traces the movement of a single patient seeking treatment for pissu (madness) from a number of healers. It is suggested that this movement of the patient among a variety of treatment systems allows a fluidity of diagnosis which prevents any one explanatory system from dominating her perception of her illness. It is also argued that treatments are linked by an underlying continuity of process, in which the personal antecedents of the illness are reinterpreted in terms of public representations of affliction and in which all treatments phrase illness most basically in terms of excess and imbalance.This paper was originally represented to an Anthropology Department colloquium at the University of Massachusetts, Boston, in the fall of 1977. I would like to thank the following people for reading and commenting on an earlier version of the paper: H. L. Seneviratne, Brenda Beck, David Landy, Nancy Waxler, Arthur Kleinman, Charles Ducey, Daniel Brown, John McCreery, and Allan Meyers.     

Risk factors of peripheral arterial disease: a case control study in Sri Lanka

Background

Peripheral artery disease (PAD) is an important global health problem and contributes to notable proportion of morbidity and mortality. This particular manifestation of systemic atherosclerosis is largely under diagnosed and undertreated. For sustainable preventive strategies in a country, it is mandatory to identify country-specific risk factors. We intended to assess the risk factors of PAD among adults aged 40–74 years.

Methods

This case control study was conducted in 2012–2013 in Sri Lanka. Seventy-nine cases and 158 controls in the age group of 40–74 years were selected for the study in order to have case to control ratio 1:2. The criterion for selecting cases and control was based on Ankle brachial pressure index (ABPI). Cases were selected from those who had ABPI 0.85 or less (ABPI ≤0.85) in either lower limb. Controls were selected from those ABPI score between 1.18 and 1.28 in both lower limbs. Only newly identified individuals with PAD were selected as cases. Controls were selected from the same geographical location and within the 5 year age group as cases.

Results

The history of diabetes mellitus more than 10 years (OR 5.8, 95% CI 2.2–14.2), history of dyslipidemia for more than 10 years (OR 4.9, 95% CI 2.1–16.2), history of hypertension for more than 10 years (OR 3.8, 95% CI 1.8–12.7) and smoking (OR 2.9, 95% CI 1.2–6.9), elevated HsCRP (OR 3.7, 95% CI 1.2–12.0) and hyperhomocysteinemia (OR 3.0, 95% CI 1.1–8.1) were revealed as country specific significant risk factor of PAD.

Conclusions

Diabetes mellitus, hypertension, dyslipidemia, smoking as well as elevated homocysteine and HsCRP found as risk factors of PAD. Longer the duration or higher level exposure to these risk factors has increased the risk of PAD. These findings emphasis the need for routine screening of PAD among patients with the identified risk factors.

     

Outcomes and moderators of a preventive school-based mental health intervention for children affected by war in Sri Lanka: a cluster randomized trial

We aimed to examine outcomes, moderators and mediators of a preventive school-based mental health intervention implemented by paraprofessionals in a war-affected setting in northern Sri Lanka. A cluster randomized trial was employed. Subsequent to screening 1,370 children in randomly selected schools, 399 children were assigned to an intervention (n=199) or waitlist control condition (n=200). The intervention consisted of 15 manualized sessions over 5 weeks of cognitive behavioral techniques and creative expressive elements. Assessments took place before, 1 week after, and 3 months after the intervention. Primary outcomes included post-traumatic stress disorder (PTSD), depressive, and anxiety symptoms. No main effects on primary outcomes were identified. A main effect in favor of intervention for conduct problems was observed. This effect was stronger for younger children. Furthermore, we found intervention benefits for specific subgroups. Stronger effects were found for boys with regard to PTSD and anxiety symptoms, and for younger children on pro-social behavior. Moreover, we found stronger intervention effects on PTSD, anxiety, and function impairment for children experiencing lower levels of current war-related stressors. Girls in the intervention condition showed smaller reductions on PTSD symptoms than waitlisted girls. We conclude that preventive school-based psychosocial interventions in volatile areas characterized by ongoing war-related stressors may effectively improve indicators of psychological wellbeing and posttraumatic stress-related symptoms in some children. However, they may undermine natural recovery for others. Further research is necessary to examine how gender, age and current war-related experiences contribute to differential intervention effects.     

Seroepidemiology of dengue and other arboviruses in a natural population of toque macaques (Macaca sinica) at Polonnaruwa,Sri Lanka

A seroepidemiological study of arboviruses infecting 115 wild toque macaques (Macaca sinica) at Polonnaruwa, Sri Lanka showed a high prevalence of antibodies to dengue and Lumbo viruses. There was low seroprevalence of Chandipura (2/115) and Batai (1/115) virus antibodies, but no seropositivity to Chikungunya or Sindbis. There was no serological evidence of infection by Japanese encephalitis (JE) virus in spite of large human epidemics in the study area, indicating that toque macaques are unlikely to be an epidemiologically relevant host in the maintenance cycle of JE virus.     

Actual exclusive breastfeeding rates and determinants among a cohort of children living in Gampaha district Sri Lanka: A prospective observational study

Background

Exclusive breastfeeding (EBF) during the early months of life reduce infant morbidity and mortality. Current recommendation in Sri Lanka is to continue exclusive breastfeeding up to six months of age. Exclusive breastfeeding rates are generally assessed by the 24 recall method which overestimates the actual rates. The objective of this study was to determine actual exclusive breast feeding rates in a cohort of Sri Lankan children and to determine the reasons that lead to cessation of breastfeeding before six months of age.

Methods

From a cohort of 2215 babies born in Gampaha district, 500 were randomly selected and invited for the study. They were followed up at two (n?=?404), four (n?=?395) and six (n?=?286) months. An interviewer administered questionnaire asked about feeding history and socio-demographic characteristics. Child health development record was used to assess the growth.

Results

Exclusive breastfeeding rates at two, four and six months were 98.0%, 75.4% and 71.3% respectively. The main reasons to stop exclusive breastfeeding between two to four months was concerns regarding weight gain and between four to six months were mothers starting to work. Majority of the babies that were not exclusively breastfed still continued to have breast milk. Mothers above 30 years had lower exclusive breastfeeding rates compared to younger mothers. Second born babies had higher rates than first borns. There was no significant association between maternal education and exclusive breastfeeding rates.

Conclusions

Exclusive breastfeeding rates were high among this cohort of children. A decrease in EBF was noted between two and four months. EBF up to six months does not cause growth failure. Mothers starting to work and concerns regarding adequacy of breast milk were the major reasons to cease EBF. The actual exclusive breastfeeding rates up to six months was 65.9%.

     

Frameworks for risk communication and disease management: the case of Lyme disease and countryside users

Management of zoonotic disease is necessary if countryside users are to gain benefit rather than suffer harm from their activities, and to avoid disproportionate reaction to novel threats. We introduce a conceptual framework based on the pressure-state-response model with five broad responses to disease incidence. Influencing public behaviour is one response and requires risk communication based on an integration of knowledge about the disease with an understanding of how publics respond to precautionary advice. A second framework emphasizes how risk communication involves more than information provision and should address dimensions including points-of-intervention over time, place and audience. The frameworks are developed by reference to tick-borne Lyme borreliosis (also known as Lyme disease), for which informed precautionary behaviour is particularly relevant. Interventions to influence behaviour can be directed by knowledge of spatial and temporal variation of tick abundance, what constitutes risky behaviour, how people respond to information of varying content, and an understanding of the social practices related to countryside use. The frameworks clarify the response options and help identify who is responsible for risk communication. These aspects are not consistently understood, and may result in an underestimation of the role of land-based organizations in facilitating appropriate precautionary behaviour.     

Clinical features of dengue in a large Vietnamese cohort: intrinsically lower platelet counts and greater risk for bleeding in adults than children

Background

As dengue spreads to new geographical regions and the force of infection changes in existing endemic areas, a greater breadth of clinical presentations is being recognised. Clinical experience suggests that adults manifest a pattern of complications different from those observed in children, but few reports have described the age-related spectrum of disease in contemporaneous groups of patients recruited at the same geographical location.

Methodology/Principal Findings

Using detailed prospectively collected information from ongoing studies that encompass the full spectrum of hospitalised dengue cases admitted to a single hospital in southern Vietnam, we compared clinical and laboratory features, management, and outcome for 647 adults and 881 children with confirmed dengue. Signs of vascular leakage and shock were more frequent and more severe in children than adults, while bleeding manifestations and organ involvement were more common in adults. Additionally, adults experienced significantly more severe thrombocytopenia. Secondary infection but not serotype was independently associated with greater thrombocytopenia, although with a smaller effect than age-group. The effect of age-group on platelet count was also apparent in the values obtained several weeks after recovery, indicating that healthy adults have intrinsically lower counts compared to children.

Conclusions/Significance

There are clear distinctions between adults and children in the pattern of complications seen in association with dengue infection, and these depend partly on intrinsic age-dependent physiological differences. Knowledge of such differences is important to inform research on disease pathogenesis, as well as to encourage development of management guidelines that are appropriate to the age-groups at risk.     

Cholesterol screening of children at high risk: behavioural and psychological effects

OBJECTIVE: To assess the behavioural and psychosocial effects of screening asymptomatic children at high risk for hyperlipidemia. DESIGN: Observational study involving prospective longitudinal and cross-sectional portions. SETTING: Two tertiary care pediatric lipid clinics in Montreal. SUBJECTS: Longitudinal portion: all children aged 4 to 17 years who presented for screening at the lipid clinics between April 1990 and June 1991. Of the 56 eligible children 52 (93%) (and their mothers) agreed to participate, 34 with hyperlipidemia (case subjects) and 18 without hyperlipidemia (control subjects). Thirty-five children (67%) completed 3 assessments over 12 months. Cross-sectional portion: all children aged 4 to 17 years in whom hyperlipidemia had been diagnosed 2 to 5 years earlier at one of the lipid clinics. Of the 58 eligible children 48 (83%) (and their mothers) participated. OUTCOME MEASURES: For children, mean scores on the Child Behavior Checklist (Behavior Problems subscale) (CBCL), the Children''s Depression Inventory (CDI) and the State-Trait Anxiety Inventory for Children (STAIC); for mothers, mean scores on the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). RESULTS: In the longitudinal portion of the study, there was no significant difference between the case and control subjects in the mean CDI or STAIC scores at 1 or 12 months. At 1 month after diagnosis the case subjects in the longitudinal portion had a significantly higher mean CBCL score than the children in the cross-sectional component (p = 0.01). With the control group as the reference group, the adjusted odds ratios for a high CBCL score (greater than 62) for the case subjects were 15.5 (95% confidence interval [CI] 2.4 to 99.8) at 1 month and 15.8 (95% CI 1.1 to 223.4) at 12 months. The corresponding values for the children in the cross-sectional component were 1.3 (95% CI 0.3 to 6.2) and 5.0 (95% CI 0.5 to 50.9). CONCLUSIONS: The observed behavioural problems in children with a recent diagnosis of hyperlipidemia were independent of other risk factors, such as age and sex of child and mother''s age and BDI score. Our results suggest that identification of hyperlipidemia in children may have harmful psychological effects in the families involved. This evidence strengthens arguments for the exclusion of cholesterol measurement from the periodic health examination of children at moderately high risk.     

Attitudes and knowledge about presymptomatic genetic testing among individuals at high risk for familial,early-onset Alzheimer's disease

The study was conducted in a large Cuban family with early-onset familial Alzheimer's disease (AD). Fifty-six first-degree relatives of familial cases with AD were interviewed concerning their clinical and genetic knowledge about AD and their attitudes toward the possible use of presymptomatic genetic testing of AD. The individuals had only limited knowledge about their personal risk of developing AD. All 56 family members would use presymptomatic testing to know their own risk of AD. Confronted with a hypothetical reproductive choice, 50% would choose not to have children if they themselves had the mutation. A positive prenatal test would lead 48.2% of the participants to have an abortion, and 19.7% would continue the pregnancy regardless of the positive test result.     

Time to exhaustion and time spent at a high percentage of VO2max in severe intensity domain in children and adults

The aim of the study was to compare time spent at a high percentage of VO2max (>90% of VO2max) (ts90%), time to achieve 90% of VO2max (ta90%), and time to exhaustion (TTE) for exercise in the severe intensity domain in children and adults. Fifteen prepubertal boys (10.3 ± 0.9 years) and 15 men (23.5 ± 3.6 years) performed a maximal graded exercise to determine VO2max, maximal aerobic power (MAP) and power at ventilatory threshold (PVTh). Then, they performed 4 constant load exercises in a random order at PVTh plus 50 and 75% of the difference between MAP and PVTh (PΔ50 and PΔ75) and 100 and 110% of MAP (P100 and P110). VO2max was continuously monitored. The P110 test was used to determine maximal accumulated oxygen deficit (MAOD). No significant difference was found in ta90% between children and adults. ts90% and TTE were not significantly different between children and adults for the exercises at PΔ50 and PΔ75. However, ts90% and TTE during P100 (p < 0.05 and p < 0.01, respectively) and P110 (p < 0.001) exercises were significantly shorter in children. Children had a significantly lower MAOD than adults (34.3 ± 9.4 ml · kg vs. 53.6 ± 11.1 ml · kg). A positive relationship (p < 0.05) was obtained between MAOD and TTE values during the P100 test in children. This study showed that only for intensities at, or higher than MAP, lower ts90% in children was linked to a reduced TTE, compared to adults. Shorter TTE in children can partly be explained by a lower anaerobic capacity (MAOD). These results give precious information about exercise intensity ranges that could be used in children's training sessions. Moreover, they highlight the implication of both aerobic and anaerobic processes in endurance performances in both populations.     

Both viremia and cytokine levels associate with the lack of severe disease in secondary dengue 1 infection among adult Chinese patients

Secondary dengue infections are frequently associated with increased risk for dengue hemorrhagic fever and dengue shock syndrome. Surprisingly, we observed no dengue hemorrhagic fever cases among 353 hospitalized dengue-infected patients including 212 with primary, and 141 with secondary dengue 1 infection in China. To explore virological and immunological mechanisms which may account for this unexpected clinical observation, we assessed dengue viremia, type I interferon and inflammatory cytokine levels in these patients. While the levels of viremia and inflammatory cytokines are indistinguishable between primary and secondary infections, IFNα levels are significantly higher in primary than that in secondary infection. However, IFNα levels are positively correlated with dengue viremia levels (p<0.0001), but negatively correlated with the platelet counts (p<0.0001) and serum ALT levels (p = 0.0003). These results provide direct in vivo evidence that clinical dengue disease severity is affected by both viral and human immune factors.     

Diabetes with hypertension as risk factors for adult dengue hemorrhagic fever in a predominantly dengue serotype 2 epidemic: a case control study

Background

Dengue hemorrhagic fever (DHF) is a severe form of dengue, characterized by bleeding and plasma leakage. A number of DHF risk factors had been suggested. However, these risk factors may not be generalized to all populations and epidemics for screening and clinical management of patients at risk of developing DHF. This study explored demographic and comorbidity risk factors for DHF in adult dengue epidemics in Singapore in year 2006 (predominantly serotype 1) and in year 2007–2008 (predominantly serotype 2).

Methods

A retrospective case-control study was conducted with 149 DHF and 326 dengue fever (DF) patients from year 2006, and 669 DHF and 1,141 DF patients from year 2007–2008. Demographic and reported comorbidity data were collected from patients previously. We performed multivariate logistic regression to assess the association between DHF and demographic and co-morbidities for year 2006 and year 2007–2008, respectively.

Results

Only Chinese (adjusted odds ratio [AOR] = 1.90; 95% confidence interval [CI]: 1.01–3.56) was independently associated with DHF in year 2006. In contrast, age groups of 30–39 years (AOR = 1.41; 95% CI:1.09–1.81), 40–49 years (AOR = 1.34; 95% CI:1.09–1.81), female (AOR = 1.57; 95% CI:1.28–1.94), Chinese (AOR = 1.67; 95% CI:1.24–2.24), diabetes (AOR = 1.78; 95% CI:1.06–2.97), and diabetes with hypertension (AOR = 2.16; 95%CI:1.18–3.96) were independently associated with DHF in year 2007–2008. Hypertension was proposed to have effect modification on the risk of DHF outcome in dengue patients with diabetes. Chinese who had diabetes with hypertension had 2.1 (95% CI:1.07–4.12) times higher risk of DHF compared with Chinese who had no diabetes and no hypertension.

Conclusions

Adult dengue patients in Singapore who were 30–49 years, Chinese, female, had diabetes or diabetes with hypertension were at greater risk of developing DHF during epidemic of predominantly serotype 2. These risk factors can be used to guide triaging of patients who require closer clinical monitoring and early hospitalization in Singapore, when confirmed in more studies.     

Diagnosis of latent tuberculosis infection in healthy young adults in a country with high tuberculosis burden and BCG vaccination at birth

ABSTRACT: BACKGROUND: One third of the world's population is thought to have latent tuberculosis infection (LTBI) with the potential for subsequent reactivation of disease. To better characterize this important population, studies comparing Tuberculin Skin Test (TST) and the new interferon-gamma release assays including QuantiFERON(R)-TB Gold In-Tube (QFT-GIT) have been conducted in different parts of the world, but most of these have been in countries with a low incidence of tuberculosis (TB). OBJECTIVE: To evaluate the use of QFT-GIT assay as compared with TST in the diagnosis of LTBI in a country with a high burden of TB and routine BCG vaccination at birth. METHODS: Healthy medical and paramedical male students at the Faculty of Medicine, Addis Ababa University, Ethiopia were enrolled into the study from December 2008 to February 2009. The TST and QFTG-IT assay were performed using standard methods. RESULTS: The mean age of the study participants was 20.9 years. From a total of 107 study participants, 46.7% (95%CI: 37.0% to 56.6%) had a positive TST result (TST greater than or equal to 10 mm), 43.9% (95%CI: 34.3% to 53.9%) had a positive QFT-GIT assay result and 44.9% (95%CI: 35.2% to 54.8%) had BCG scar. There was strong agreement between TST (TST greater than or equal to 10mm) and QFT-GIT assay (Kappa = 0.83, p value=0.000). CONCLUSION: The TST and QFT-GIT assay show similar efficacy for the diagnosis of LTBI in healthy young adults residing in Ethiopia, a country with high TB incidence.