Birth Patterns in the Aftermath of the 1918 Influenza Pandemic in India: The Case of Madras City.

This paper examines the timing of one-time fluctuations in births subsequent to the 1918 influenza pandemic in Madras (now Chennai), India. After seasonally decomposing key demographic aggregates, we identified abrupt one-time fluctuations in excess births, deaths, and infant deaths. We found a contemporaneous spike in excess deaths and infant deaths and a 40-week lag between the spike in deaths and a subsequent deficit in births. The results suggest that India experienced the same kind of short-term postpandemic "baby bust" that was observed in the United States and other countries. Identifying the mechanisms underlying this widespread phenomenon remains an open question and an important topic for future research.

Human Passage of Schistosoma incognitum, Tamil Nadu, India, and Review of Autochthonous Schistosomiasis, South Asia.

A fecal survey in Tamil Nadu, India, revealed 2 persons passed schistosome eggs, later identified as Schistosoma incognitum, a parasite of pigs, dogs, and rats. We investigated those cases and reviewed autochthonous schistosomiasis cases from India and Nepal. Whether the 2 new cases represent true infection or spurious passage is undetermined.

Community and health worker perspectives on malaria in Meghalaya, India: covering the last mile of elimination by 2030.

BACKGROUND: Malaria remains a public health problem in regions of Northeastern India because of favourable bio-geographic transmission conditions, poor access to routine healthcare, and inadequate infrastructure for public health and disease prevention. This study was undertaken to better understand community members' and health workers' perceptions of malaria, as well as their knowledge, attitudes, and prevention practices related to the disease in Meghalaya state. METHODS: The study included participants from three malaria endemic districts: West Khasi Hills, West Jaiñtia Hills, and South Garo Hills from 2019 to 2021. A total of 82 focus group discussions (FGD) involving 694 community members and 63 in-depth interviews (IDI) with health personnel and traditional healers residing within the three districts were conducted. A thematic content analysis approach was employed, using NVivo12 software for data management. RESULTS: Most participants reported a perceived reduction in malaria during recent years, attributing this to changes in attitudes and behaviours in health seeking, and to more effective government interventions. Local availability of testing and treatment, and an improved, more responsive health system contributed to changing attitudes. Long-lasting insecticidal nets (LLINs) were largely preferred over indoor residual spraying (IRS), as LLINs were perceived to be effective and more durable. Community members also reported using personal protective measures such as applying repellents, burning neem tree leaves, straw/egg trays, wearing long sleeve clothes, and applying ointments or oils to protect themselves from mosquito bites. While most participants acknowledged the role of mosquitoes in malaria transmission, other conditions that are not mosquito-borne were also attributed to mosquitoes by some participants. The communities surveyed have largely shifted from seeking treatment for malaria from traditional healers to using public facilities, although some participants reported switching between the two or using both simultaneously. Improved understanding of cerebral malaria, which some participants previously attributed to mental illness due to 'bad spirits', is an example of how cultural and ritualistic practices have changed. CONCLUSION: The findings reveal diverse perceptions among community members regarding malaria, its prevention, practices to prevent mosquito-transmitted diseases, and their opinions about the healthcare system. A key finding was the shift in malaria treatment-seeking preferences of community members from traditional healers to the public sector. This shift highlights the changing dynamics and increasing acceptance of modern healthcare practices for malaria treatment and prevention within tribal and/or indigenous communities. By recognizing these evolving attitudes, policymakers and healthcare providers can better tailor their interventions and communication strategies to more effectively address ongoing needs and concerns as India faces the 'last mile' in malaria elimination.

Technologies for strengthening immunization coverage in India: a systematic review.

Background: Immunization coverage varies across India in different settings, geographic areas and populations. Technologies for improving immunization access can reduce disparities in coverage. This systematic review, which follows PRISMA guidelines, aims to examine the technologies for strengthening immunization coverage in India. Methods: Studies published between January 1, 2011 and July 31, 2021 were searched in Medline (through PubMed), Cochrane Library and Google Scholar. All observational and experimental studies, except qualitative studies, were included. Studies published in the English language and related to technologies for strengthening immunization, conducted on children, pregnant women, adults, elderly, healthcare personnel, caregivers and vulnerable populations across all Indian settings were included. Non-English articles, protocols, commentaries, letters, abstracts, correspondence, opinion articles, modelling, narrative and systematic reviews were excluded. Two reviewers screened studies independently, extracted data in a standardized sheet and appraised the study quality using the Mixed Methods Appraisal Tool. The primary outcome was technologies that improved immunization coverage. The protocol is registered with OSF (https://osf.io/r42gm). Findings: 6592 titles and abstracts were screened, and data extracted from 23 India-specific studies. Quality of 22/23 studies was average or above. Technologies identified included reminder systems, capacity building, community engagement and wearable technologies. Automated incentivised mobile phone reminders, immunization due-list, computerized data tracking, community mobilization and campaigns improved vaccine coverage, although effectiveness of some varied viz., reminder systems, and across states. Newer technologies included the Jyotigram Yojana, Digital Near-field Communication Pendants, "Reaching Every District" Programme and the "My Village My Home" tool. Interpretation: Technologies for improving immunization systems, capacity building and community engagement were effective. Newer technologies on vaccine delivery, mapping and cold chain logistics were not evaluated in India or were ineffective. There were limited studies in populations other than children and pregnant women. Future work is needed to evaluate the effectiveness of identified technologies across diverse settings. Funding: No funding was received for preparing this manuscript.

Understanding COVID-19 vaccine hesitancy in Meghalaya, India: Multiple correspondence and agglomerative hierarchical cluster analyses.

Meghalaya, a state in the northeastern region of India, had a markedly low vaccine uptake compared to the other states in the country when COVID-19 vaccines were being rolled out in 2021. This study aimed to characterize the distinct vaccine-hesitant subpopulations in healthcare and community settings in Meghalaya state in the early days of the vaccination program. We used data from a cross-sectional survey that was administered to 200 healthcare workers (HCWs) and 200 community members, who were a priori identified as 'vaccine-eligible' and 'vaccine-hesitant,' in Shillong city, Meghalaya, in May 2021. The questionnaire collected information on participants' sociodemographic characteristics, COVID-19 history, and presence of medical comorbidities. Participants were also asked to provide a dichotomous answer to a set of 19 questions, probing the reasons for their hesitancy towards COVID-19 vaccines. A multiple correspondence analysis, followed by an agglomerative hierarchical cluster analysis, was performed to identify the distinct clusters of vaccine-hesitant participants. We identified seven clusters: indecisive HCWs (n = 71), HCWs skeptical of COVID-19 and COVID-19 vaccines (n = 128), highly educated male tribal/clan leaders concerned about infertility and future pregnancies (n = 14), less educated adults influenced by leaders and family (n = 47), older adults worried about vaccine safety (n = 76), middle-aged adults without young children (n = 56), and highly educated ethnic/religious minorities with misinformation (n = 8). Across all the clusters, perceived logistical challenges associated with receiving the vaccine was identified as a common factor contributing to vaccine hesitancy. Our study findings provide valuable insights for local and state health authorities to effectively target distinct subgroups of vaccine-hesitant populations with tailored health messaging, and also call for a comprehensive approach to address the common drivers of vaccine hesitancy in communities with low vaccination rates.

Community and health worker perspectives on malaria in Meghalaya, India: Covering the last mile of elimination by 2030.

Background: Malaria remains a public health problem in regions of northeastern India due to favourable bio-geographic transmission conditions, poor access to routine healthcare, and inadequate public health and healthcare infrastructure. This study was undertaken to better understand community members' and health workers' perceptions of malaria, as well as their knowledge, attitudes, and prevention practices related to the disease in Meghalaya state. Methods: The study included participants from three malaria endemic districts: West Khasi Hills, West Jaiñtia Hills, and South Garo Hills from 2019 to 2021. A total of 82 focus group discussions (FGD) with 694 community members and 63 in-depth interviews (IDI) with health personnel and traditional healers residing within the three districts were conducted. A thematic content analysis approach was employed, and NVivo12 software was utilized for data management. Results: Most participants reported a perceived reduction in malaria during recent years and attributed this to changing attitudes and behaviours in health seeking behaviour and effective government interventions. Local availability of testing and treatment, and an improved, more responsive health system contributed to changing attitudes. Long-lasting insecticidal nets (LLINs) were largely preferred over indoor residual spraying (IRS), as LLINs were perceived to be effective and more durable. Community members also reported using personal protective measures such as applying repellents, burning straw/egg trays, wearing long sleeve clothes, and applying ointments or oils to protect themselves from mosquito bites. While most participants acknowledged the role of mosquitoes in malaria transmission, other conditions that are not mosquito-borne were also attributed to mosquitoes by some participants. The communities surveyed have largely shifted from seeking traditional healers to using public facilities, although some participants reported switching between the two or using both simultaneously. Using the example of improved understanding of cerebral malaria which was previously attributed to mental illness due to 'bad spirits', participants explained how cultural and ritualistic practices had changed. Conclusions: Our findings reveal diverse perceptions among community members regarding malaria, its prevention, practices to prevent mosquito-transmitted diseases, and their opinions about the health system. A key finding was the shift in malaria treatment seeking preferences of community members from traditional healers to the public sector. This shift highlights the changing dynamics and increasing acceptance of modern healthcare practices for malaria treatment and prevention within tribal and/or indigenous communities. By recognizing these evolving attitudes, policymakers and healthcare providers can better tailor their interventions and communication strategies to more effectively address ongoing needs and concerns as India faces the 'last mile' in malaria elimination.

Social network and household exposure explain the use of malaria prevention measures in rural communities of Meghalaya, India.

Malaria remains a global concern despite substantial reduction in incidence over the past twenty years. Public health interventions to increase the uptake of preventive measures have contributed to this decline but their impact has not been uniform. To date, we know little about what determines the use of preventive measures in rural, hard-to-reach populations, which are crucial contexts for malaria eradication. We collected detailed interview data on the use of malaria preventive measures, health-related discussion networks, individual characteristics, and household composition in ten tribal, malaria-endemic villages in Meghalaya, India in 2020-2021 (n=1,530). Employing standard and network statistical models, we found that social network and household exposure were consistently positively associated with preventive measure use across villages. Network and household exposure were also the most important factors explaining behaviour, outweighing individual characteristics, opinion leaders, and network size. These results suggest that real-life data on social networks and household composition should be considered in studies of health-behaviour change.

The need for a holistic approach toward pandemic control: lessons from a cross-sectional study on COVID-19 in Meghalaya, India.

We conducted a community-based cross-sectional survey of 416 participants from Meghalaya, India to assess knowledge, perceptions, and practices toward recommended COVID-19 preventive measures, and to explore health-seeking behavior and stigma during early phase of the pandemic. Most participants had knowledge of the signs and symptoms of COVID-19 (94%) and its spread (96%), and reported positive behavior change such as handwashing ≥ 6 times/day (41% pre-COVID-19 vs. 81% during COVID-19, P < 0.001), sneezing or coughing into sleeves (65% pre-COVID-19 vs. 89% during COVID-19, P < 0.001) and staying home if having flu-like symptoms (44% pre-COVID-19 vs. 94% during COVID-19, P < 0.001). We found delayed healthcare seeking for non-COVID-19 illnesses (16%). Fear of losing life was reported by 26% participants, as was discrimination toward migrant returnees, with 35% blaming returnees for the spread of COVID-19. We highlight the need for a holistic approach toward pandemic control, including social and mental health interventions, in public health strategies.

Soil-transmitted helminth infections after mass drug administration for lymphatic filariasis in rural southern India.

OBJECTIVES: Targeted deworming is the current strategy for control of morbidity associated with soil-transmitted helminths (STH) among at-risk populations: preschool-aged children, school-aged children and women of childbearing age. We report the prevalence and intensity of STH in a district after lymphatic filariasis (LF) mass drug administration (MDA) in southern India where albendazole was co-administered from 2001. METHODS: Children aged 2 to 15 years and adults (defined as ≥15 years) in a rural administrative block of Tamil Nadu were recruited using a probability proportional to size method. Stool samples were screened and eggs per gram (EPG) determined by Kato-Katz method. Multilevel logistic regression (MLR) and multilevel negative binomial regression (MNBR) analyses were used to identify factors associated with infection and intensity, respectively. RESULTS: Of 862 participants who provided samples, 60 (7.0%; 95% confidence interval (CI): 5.3-8.7) were positive for STH with a predominance of hookworm infections (n = 57, 6.6%; 95% CI: 5.0-8.3). Increasing age (odds ratio (OR): 1.09; 95% CI: 1.04-1.15) and regular usage of the toilet (OR: 0.32; 95% CI: 0.12-0.88) were independently associated with hookworm infection and age was significantly associated with increasing intensity of hookworm infection (infection intensity ratio (IIR): 1.28; 95% CI: 1.19-1.37). A brief review of STH prevalence in endemic settings before and after the stoppage of LF MDA indicated that, in most settings, a substantial reduction in STH prevalence is seen. CONCLUSION: Community-wide MDA in all age groups in these post-LF MDA districts with low prevalence and light intensity infections could result in transmission interruption of STH.

Household and individual level risk factors associated with declining malaria incidence in Meghalaya, India: implications for malaria elimination in low-endemic settings.

BACKGROUND: A detailed analysis of household and individual level Plasmodium infection patterns in two low-endemic districts of Meghalaya was undertaken to better understand the epidemiology of malaria in northeast India. METHODS: Socio-demographic and behavioural information from residents (aged 1-69 years) of households were collected through pre-tested, questionnaire conducted in 2018 and 2019. Blood samples collected from participants were tested for Plasmodium falciparum and/or Plasmodium vivax infection using rapid diagnostic test, microscopy and PCR. Plasma samples from a subset of participants were analysed for antibodies against thirteen P. falciparum and four P. vivax antigens. Associations between household and individual level risk factors, and Plasmodium infections were evaluated using multilevel logistic regression models. RESULTS: A total of 2753 individuals from 827 households were enrolled in 2018, and 834 individuals from 222 households were enrolled in 2019. Of them, 33 (1.2%) were positive by PCR for P. falciparum in 2018 and none were positive for P. vivax. In 2019, no PCR-positive individuals were detected. All, but one, infections were asymptomatic; all 33 infections were sub-microscopic. Reported history of malaria in the past 12 months (OR = 8.84) and history of travel in the past 14 days (OR = 10.06) were significantly associated with Plasmodium infection. A significant trend of increased seropositivity with age was noted for all 17 antigens. Although adults (≥ 18 years) consistently had the highest seropositivity rates, a sizeable proportion of under-five children were also found to be seropositive. Almost all individuals (99.4%) reported sleeping under an insecticide-treated bed-net, and household indoor residual spray coverage in the 12 months preceding the survey was low (23%). Most participants correctly identified common signs and symptoms of malaria, i.e., fever (96.4%), headache (71.2%), chills (83.2%) and body-ache (61.8%). Almost all participants (94.3%) used government-provided services for treatment of malaria. CONCLUSION: This study explored the epidemiology of malaria in two communities in Meghalaya, India, in the context of declining transmission. The presence of widespread asymptomatic infections and seropositivity among under-five children suggest that low-level Plasmodium transmission persists in this region. Implications of the study findings for malaria elimination efforts in low-transmission settings are discussed.

Epidemiology of soil transmitted helminths and risk analysis of hookworm infections in the community: Results from the DeWorm3 Trial in southern India.

Since 2015, India has coordinated the largest school-based deworming program globally, targeting soil-transmitted helminths (STH) in ~250 million children aged 1 to 19 years twice yearly. Despite substantial progress in reduction of morbidity associated with STH, reinfection rates in endemic communities remain high. We conducted a community based parasitological survey in Tamil Nadu as part of the DeWorm3 Project-a cluster-randomised trial evaluating the feasibility of interrupting STH transmission at three geographically distinct sites in Africa and Asia-allowing the estimation of STH prevalence and analysis of associated factors. In India, following a comprehensive census, enumerating 140,932 individuals in 36,536 households along with geospatial mapping of households, an age-stratified sample of individuals was recruited into a longitudinal monitoring cohort (December 2017-February 2018) to be followed for five years. At enrolment, a total of 6089 consenting individuals across 40 study clusters provided a single adequate stool sample for analysis using the Kato-Katz method, as well as answering a questionnaire covering individual and household level factors. The unweighted STH prevalence was 17.0% (95% confidence interval [95%CI]: 16.0-17.9%), increasing to 21.4% when weighted by age and cluster size. Hookworm was the predominant species, with a weighted infection prevalence of 21.0%, the majority of which (92.9%) were light intensity infections. Factors associated with hookworm infection were modelled using mixed-effects multilevel logistic regression for presence of infection and mixed-effects negative binomial regression for intensity. The prevalence of both Ascaris lumbricoides and Trichuris trichiura infections were rare (<1%) and risk factors were therefore not assessed. Increasing age (multivariable odds ratio [mOR] 21.4, 95%CI: 12.3-37.2, p<0.001 for adult age-groups versus pre-school children) and higher vegetation were associated with an increased odds of hookworm infection, whereas recent deworming (mOR 0.3, 95%CI: 0.2-0.5, p<0.001) and belonging to households with higher socioeconomic status (mOR 0.3, 95%CI: 0.2-0.5, p<0.001) and higher education level of the household head (mOR 0.4, 95%CI: 0.3-0.6, p<0.001) were associated with lower odds of hookworm infection in the multilevel model. The same factors were associated with intensity of infection, with the use of improved sanitation facilities also correlated to lower infection intensities (multivariable infection intensity ratio [mIIR] 0.6, 95%CI: 0.4-0.9, p<0.016). Our findings suggest that a community-based approach is required to address the high hookworm burden in adults in this setting. Socioeconomic, education and sanitation improvements alongside mass drug administration would likely accelerate the drive to elimination in these communities. Trial Registration: NCT03014167.

Oral corticosteroid prescription patterns for asthma in France, Germany, Italy and the UK.

Oral corticosteroids (OCS) are used to manage asthma exacerbations and severe, uncontrolled asthma, but OCS use is associated with adverse effects. We aimed to describe the patterns of OCS use in the real-world management of patients with asthma in western Europe.We used electronic medical records from databases in France, Germany, Italy and the United Kingdom from July 2011 through February 2018. Patients aged ≥12 years with an asthma diagnosis, at least one non-OCS asthma medication within ±6 months of diagnosis, and available data ≥6 months prior to and ≥90 days after cohort entry were included. High OCS use was defined as OCS ≥450 mg prescribed in a 90-day window during follow-up. Baseline characteristics and OCS use during follow-up were described overall and by OCS use status.Of 702 685 patients with asthma, 14-44% were OCS users and 6-9% were high OCS users at some point during follow-up. Annual prevalence of high OCS use across all countries was ∼3%. High OCS users had a mean of between one and three annual OCS prescriptions, with an average daily OCS dosage of 1.3-2.2 mg. For patients who continued to meet the high-use definition, daily OCS exposure was generally stable at 5.5-7.5 mg for ≥2 years, increasing the risk of adverse effects.Our study demonstrates that OCS use is relatively common across the four studied European countries. Data from this study may provide decisive clinical insights to inform primary care physicians and specialists involved in the management of severe, uncontrolled asthma.

Prediction of hookworm prevalence in southern India using environmental parameters derived from Landsat 8 remotely sensed data.

Soil-transmitted helminth infections propagate poverty and slow economic growth in low-income countries. As with many other neglected tropical diseases, environmental conditions are important determinants of soil-transmitted helminth transmission. Hence, remotely sensed data are commonly utilised in spatial risk models intended to inform control strategies. In the present study, we build upon the existing modelling approaches by utilising fine spatial resolution Landsat 8 remotely sensed data in combination with topographic variables to predict hookworm prevalence in a hilly tribal area in southern India. Hookworm prevalence data collected from two field surveys were used in a random forest model to investigate the predictive capacity of 15 environmental variables derived from two remotely sensed images acquired during dry and rainy seasons. A variable buffer radius (100-1000 m) was applied to the point-prevalence locations in order to integrate environmental conditions around the village centroids into the modelling approach and understand where transmission is more likely. Elevation and slope were the most important variables in the models, with lower elevation and higher slope correlating with higher transmission risk. A modified normalised difference water index was among other recurring important variables, likely responsible for some seasonal differences in model performance. The 300 m buffer distance produced the best model performance in this setting, with another spike at 700 m, and a marked drop-off in R2 values at 1000 m. In addition to assessing a large number of environmental correlates with hookworm transmission, the study contributes to the development of standardised methods of spatial linkage of continuous environmental data with point-based disease prevalence measures for the purpose of spatially explicit risk profiling.

Impact of Different Sampling Schemes for Decision Making in Soil-Transmitted Helminthiasis Control Programs.

Starting and stopping preventive chemotherapy (PC) for soil-transmitted helminthiasis is typically based on the prevalence of infection as measured by Kato-Katz (KK) fecal smears. Kato-Katz-based egg counts can vary highly over repeated stool samples and smears. Consequentially, the sensitivity of KK-based surveys depends on the number of stool samples per person and the number of smears per sample. Given finite resources, collecting multiple samples and/or smears means screening fewer individuals, thereby lowering the statistical precision of prevalence estimates. Using population-level data from various epidemiological settings, we assessed the performance of different sampling schemes executed within the confines of the same budget. We recommend the use of single-slide KK for determining prevalence of moderate-to-heavy intensity infection and policy decisions for starting and continuing PC; more sensitive sampling schemes may be required for policy decisions involving stopping PC. Our findings highlight that guidelines should include specific guidance on sampling schemes.

Assessing the feasibility of interrupting the transmission of soil-transmitted helminths through mass drug administration: The DeWorm3 cluster randomized trial protocol.

Current control strategies for soil-transmitted helminths (STH) emphasize morbidity control through mass drug administration (MDA) targeting preschool- and school-age children, women of childbearing age and adults in certain high-risk occupations such as agricultural laborers or miners. This strategy is effective at reducing morbidity in those treated but, without massive economic development, it is unlikely it will interrupt transmission. MDA will therefore need to continue indefinitely to maintain benefit. Mathematical models suggest that transmission interruption may be achievable through MDA alone, provided that all age groups are targeted with high coverage. The DeWorm3 Project will test the feasibility of interrupting STH transmission using biannual MDA targeting all age groups. Study sites (population ≥80,000) have been identified in Benin, Malawi and India. Each site will be divided into 40 clusters, to be randomized 1:1 to three years of twice-annual community-wide MDA or standard-of-care MDA, typically annual school-based deworming. Community-wide MDA will be delivered door-to-door, while standard-of-care MDA will be delivered according to national guidelines. The primary outcome is transmission interruption of the STH species present at each site, defined as weighted cluster-level prevalence ≤2% by quantitative polymerase chain reaction (qPCR), 24 months after the final round of MDA. Secondary outcomes include the endline prevalence of STH, overall and by species, and the endline prevalence of STH among children under five as an indicator of incident infections. Secondary analyses will identify cluster-level factors associated with transmission interruption. Prevalence will be assessed using qPCR of stool samples collected from a random sample of cluster residents at baseline, six months after the final round of MDA and 24 months post-MDA. A smaller number of individuals in each cluster will be followed with annual sampling to monitor trends in prevalence and reinfection throughout the trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03014167.

Evaluating the sustainability, scalability, and replicability of an STH transmission interruption intervention: The DeWorm3 implementation science protocol.

Hybrid trials that include both clinical and implementation science outcomes are increasingly relevant for public health researchers that aim to rapidly translate study findings into evidence-based practice. The DeWorm3 Project is a series of hybrid trials testing the feasibility of interrupting the transmission of soil transmitted helminths (STH), while conducting implementation science research that contextualizes clinical research findings and provides guidance on opportunities to optimize delivery of STH interventions. The purpose of DeWorm3 implementation science studies is to ensure rapid and efficient translation of evidence into practice. DeWorm3 will use stakeholder mapping to identify individuals who influence or are influenced by school-based or community-wide mass drug administration (MDA) for STH and to evaluate network dynamics that may affect study outcomes and future policy development. Individual interviews and focus groups will generate the qualitative data needed to identify factors that shape, contextualize, and explain DeWorm3 trial outputs and outcomes. Structural readiness surveys will be used to evaluate the factors that drive health system readiness to implement novel interventions, such as community-wide MDA for STH, in order to target change management activities and identify opportunities for sustaining or scaling the intervention. Process mapping will be used to understand what aspects of the intervention are adaptable across heterogeneous implementation settings and to identify contextually-relevant modifiable bottlenecks that may be addressed to improve the intervention delivery process and to achieve intervention outputs. Lastly, intervention costs and incremental cost-effectiveness will be evaluated to compare the efficiency of community-wide MDA to standard-of-care targeted MDA both over the duration of the trial and over a longer elimination time horizon.

Geographical distribution of soil transmitted helminths and the effects of community type in South Asia and South East Asia - A systematic review.

BACKGROUND: Soil-transmitted helminth (STH) infections are among the most prevalent neglected tropical diseases (NTD) worldwide. Since the publication of the WHO road map to combat NTD in 2012, there has been a renewed commitment to control STH. In this study, we analysed the geographical distribution and effect of community type on prevalence of hookworm, Trichuris and Ascaris in south Asia and south east Asia. METHODOLOGY: We conducted a systematic review of open-access literature published in PubMed Central and the Global Atlas of Helminth Infection. A total of 4182 articles were available and after applying selection criteria, 174 studies from the region were retained for analysis. PRINCIPAL FINDINGS: Ascaris was the commonest STH identified with an overall prevalence of 18% (95% CI, 14-23%) followed by Trichuris (14%, 9-19%) and hookworm (12%, 9-15%). Hookworm prevalence was highest in Laos, Vietnam and Cambodia. We found a geographical overlap in countries with high prevalence rates for Trichuris and Ascaris (Malaysia, Philippines, Myanmar, Vietnam and Bangladesh). When the effect of community type was examined, prevalence rates of hookworm was comparable in rural (19%, 14-24%) and tribal communities (14%, 10-19%). Tribal communities, however, showed higher prevalence of Trichuris (38%, 18-63%) and Ascaris (32%, 23-43%) than rural communities (13%, 9-20% and 14%, 9-20% respectively). Considerable between and within country heterogeneity in the distribution of STH (I2 >90%) was also noted. When available data from school aged children (SAC) were analysed, prevalence of Ascaris (25% 16-31%) and Trichuris (22%, 14-34%) were higher than among the general population while that of hookworm (10%, 7-16%) was comparable. CONCLUSIONS/SIGNIFICANCE: Our analysis showed significant variation in prevalence rates between and within countries in the region. Highlighting the importance of community type in prevalence and species mix, we showed that tribal and rural communities had higher hookworm infections than urban communities and for ascariasis and trichuriasis, tribal populations had higher levels of infection than rural populations. We also found a higher prevalence of ascariasis and trichuriasis in SAC compared to the general population but comparable levels of hookworm infections. These key findings need to be taken into account in planning future MDA and other interventions.

The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants.

BACKGROUND: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. METHODS: Infants 5weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5mg), probiotic (1010Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14weeks of age based on detection of VP6-specific IgA at ≥20U/ml in previously seronegative infants or a fourfold rise in concentration. RESULTS: The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): -1.4%, 16.2%), p=0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: -4.4%, 13.2%), p=0.272). 16 serious adverse events were recorded, none related to study interventions. CONCLUSIONS: Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation. TRIAL REGISTRATION: The trial was registered in India (CTRI/2012/05/002677).

Temporal trends of intestinal parasites in patients attending a tertiary care hospital in south India: A seven-year retrospective analysis.

BACKGROUND & OBJECTIVES: Intestinal parasitic infections and their associated complications are a major cause of morbidity in the developing world. This retrospective study was done to assess the prevalence of intestinal parasitic infections among patients in a tertiary healthcare setting and to analyze age-, gender- and time-related trends in the prevalence of these intestinal parasites over a seven year period (2006-2012). METHODS: The presence of various intestinal parasites in a tertiary care setting over a seven year period in different age groups was determined by performing routine stool microscopy. Modified acid-fast staining was performed for stool samples collected from children less than five years of age for the detection of intestinal coccidian parasites. Statistical analysis was carried out to analyze age-related trends in relation to the prevalence of commonly detected intestinal parasites. Seasonal fluctuations in parasite prevalence were evaluated by performing harmonic regression analysis. RESULTS: A total of 257,588 stool samples were received over the seven year period for examination. The highest percentage of intestinal parasites was in the 6-10 yr age group. Among the intestinal parasites, Giardia intestinalis had the highest prevalence across most age groups, except in those above 60 yr of age where hookworm became more prevalent. A significant decreasing trend with age was observed for G. intestinalis, whereas for hookworm and Strongyloides stercoralis, an increasing trend with age was seen. Significant linear temporal trends were observed for parasites such as G. intestinalis, Entamoeba histolytica and Ascaris lumbricoides. INTERPRETATION & CONCLUSIONS: While G. intestinalis was more common in the younger age groups, certain soil-transmitted helminths such as hookworm and S. stercoralis showed a higher prevalence in the older populations. Significant temporal trends and seasonality were observed for some of the common intestinal parasites.

Identifying optimal threshold statistics for elimination of hookworm using a stochastic simulation model.

BACKGROUND: There is an increased focus on whether mass drug administration (MDA) programmes alone can interrupt the transmission of soil-transmitted helminths (STH). Mathematical models can be used to model these interventions and are increasingly being implemented to inform investigators about expected trial outcome and the choice of optimum study design. One key factor is the choice of threshold for detecting elimination. However, there are currently no thresholds defined for STH regarding breaking transmission. METHODS: We develop a simulation of an elimination study, based on the DeWorm3 project, using an individual-based stochastic disease transmission model in conjunction with models of MDA, sampling, diagnostics and the construction of study clusters. The simulation is then used to analyse the relationship between the study end-point elimination threshold and whether elimination is achieved in the long term within the model. We analyse the quality of a range of statistics in terms of the positive predictive values (PPV) and how they depend on a range of covariates, including threshold values, baseline prevalence, measurement time point and how clusters are constructed. RESULTS: End-point infection prevalence performs well in discriminating between villages that achieve interruption of transmission and those that do not, although the quality of the threshold is sensitive to baseline prevalence and threshold value. Optimal post-treatment prevalence threshold value for determining elimination is in the range 2% or less when the baseline prevalence range is broad. For multiple clusters of communities, both the probability of elimination and the ability of thresholds to detect it are strongly dependent on the size of the cluster and the size distribution of the constituent communities. Number of communities in a cluster is a key indicator of probability of elimination and PPV. Extending the time, post-study endpoint, at which the threshold statistic is measured improves PPV value in discriminating between eliminating clusters and those that bounce back. CONCLUSIONS: The probability of elimination and PPV are very sensitive to baseline prevalence for individual communities. However, most studies and programmes are constructed on the basis of clusters. Since elimination occurs within smaller population sub-units, the construction of clusters introduces new sensitivities for elimination threshold values to cluster size and the underlying population structure. Study simulation offers an opportunity to investigate key sources of sensitivity for elimination studies and programme designs in advance and to tailor interventions to prevailing local or national conditions.