Evaluation of Molecular Assays for Diagnosis of Amoebic Liver Abscess in India with Bayesian Latent Class Analysis.

Amoebic liver abscess (ALA) is the most common extra-intestinal complication of Entamoeba histolytica, accounting for 50,000 deaths annually, and is endemic in South Asia. Diagnosis based on microscopic examination is insensitive, and serological assays are not discerning of current infections in endemic settings with high exposure. For a rapid and confirmatory laboratory diagnosis of ALA, the performance of a polymerase chain reaction (PCR), quantitative real time PCR (qPCR), digital droplet PCR (ddPCR), and a loop-mediated isothermal amplification (LAMP) assay that detects E. histolytica DNA in liver abscess pus, and a lectin antigen detection ELISA were evaluated against clinical diagnosis (based on predefined criteria) as the gold standard. Owing to the lack of a laboratory gold standard, a Bayesian latent class analysis approach was also used to determine sensitivity and specificity of these assays. In the latent class analysis, qPCR and ddPCR showed the highest sensitivity (98% and 98.1%) and specificity (both 96.6%), and although clinical diagnosis had a comparable sensitivity to qPCR and ddPCR (95.2%), poorer specificity (64.3%) was seen. Kappa agreement analysis showed that qPCR and ddPCR had a perfect agreement of 1 followed by an agreement of 0.76 (95% CI: 0.64-0.88) with PCR. Considering the performance characteristics and relative ease of setting up qPCR as well as the wide availability of qPCR equipment needed, this would be the most optimal assay for rapid, confirmatory, molecular diagnosis of ALA in the tertiary care laboratory setting in India, whereas further optimization of LAMP or antibody-based detection is required for use at smaller or secondary hospitals.

Adolescents' Perspective Regarding a Community-Wide Mass Drug Administration Program for Soil-Transmitted Helminths in India.

This study was undertaken to understand the perspective of adolescents in endemic communities of India regarding soil-transmitted helminth (STH) infections and community-wide mass drug administration (cMDA). A multicountry community-based cluster-randomized trial, the Deworm3 trial, tested the feasibility of interrupting STH transmission with cMDA, where all individuals aged 1-99 are treated empirically with albendazole. Using a guideline based on the Consolidated Framework for Implementation Research, eight focus group discussions were conducted among 57 adolescents from the trial site in India and analyzed on ATLAS.ti 8.0 software using an a priori thematic codebook. Adolescents believed that adults could be a source of STH infection because they were not routinely dewormed like the children through the national deworming program. Perceived benefits of cMDA for all were better health and increased work efficiency. Perceived barriers to adults' participation in cMDA was their mistrust about the program, fear of side effects, perceived low risk of infection, and absence during drug distribution. To encourage adult participation in cMDAs, adolescents suggested community outreach activities, engaging village influencers and health workers, and tailoring drug distribution to when adults would be available. Adolescents were confident in their ability to be change agents within their households for treatment compliance. Adolescents provided insights into potential barriers and solutions to improve adult participation in cMDA, identified best practices of cMDA delivery, and suggested that they have unique roles as change agents to increase their household participation in cMDA.

"Our desire is to make this village intestinal worm free": Identifying determinants of high coverage of community-wide mass drug administration for soil transmitted helminths in Benin, India, and Malawi.

BACKGROUND: Soil-transmitted helminth infections (STH) are associated with substantial morbidity in low-and-middle-income countries, accounting for 2.7 million disability-adjusted life years annually. Current World Health Organization guidelines recommend controlling STH-associated morbidity through periodic deworming of at-risk populations, including children and women of reproductive age (15-49 years). However, there is increasing interest in community-wide mass drug administration (cMDA) which includes deworming adults who serve as infection reservoirs as a method to improve coverage and possibly to interrupt STH transmission. We investigated determinants of cMDA coverage by comparing high-coverage clusters (HCCs) and low-coverage clusters (LCCs) receiving STH cMDA in three countries. METHODS: A convergent mixed-methods design was used to analyze data from HCCs and LCCs in DeWorm3 trial sites in Benin, India, and Malawi following three rounds of cMDA. Qualitative data were collected via 48 community-level focus group discussions. Quantitative data were collected via routine activities nested within the DeWorm3 trial, including annual censuses and coverage surveys. The Consolidated Framework for Implementation Research (CFIR) guided coding, theme development and a rating process to determine the influence of each CFIR construct on cMDA coverage. RESULTS: Of 23 CFIR constructs evaluated, we identified 11 constructs that differentiated between HCCs and LCCs, indicating they are potential drivers of coverage. Determinants differentiating HCC and LCC include participant experiences with previous community-wide programs, communities' perceptions of directly observed therapy (DOT), perceptions about the treatment uptake behaviors of neighbors, and women's agency to make household-level treatment decisions. CONCLUSION: The convergent mixed-methods study identified barriers and facilitators that may be useful to NTD programs to improve cMDA implementation for STH, increase treatment coverage, and contribute to the successful control or elimination of STH. TRIAL REGISTRATION: The parent trial was registered at clinicaltrials.gov (NCT03014167).

Remote evaluation of STH program coverage: Experiences from the DeWorm3 study, India.

BACKGROUND: The DeWorm3 trial is a multi-country study testing the feasibility of interrupting transmission of soil-transmitted helminths by community-wide mass drug administration (cMDA). Treatment coverage during cMDA delivery was validated by in-person coverage evaluation surveys (CES) after each round of treatment. A mobile phone-based CES was carried out in India when access to households was restricted during the COVID-19 lockdown. METHODS: Two focus group discussions were conducted with the survey implementers to document their experiences of conducting phone-based CES via mobile-phone voice calls. PRINCIPAL FINDINGS: In the phone-based CES, only 56% of sampled households were reached compared to 89% during the in-person CES (89%). This was due to phone numbers being wrongly recorded, or calls being unanswered leading to a higher number of households that had to be sampled in order to achieve the sample size of 2,000 households in phone-based CES compared in-person CES (3,600 and 2,352 respectively). Although the phone-based CES took less time to complete than in person coverage evaluations, the surveyors highlighted the lack of gender representation among phone survey participants as it was mostly men who answered calls and were then interviewed. The surveyors also mentioned that eliciting responses to open-ended questions and confirming treatment compliance from every member of the household was challenging during phone based CES. These observations were confirmed by analysing the survey participation data which showed women's participation in CES was significantly lower in phone-based CES (66%) compared to in-person CES (94%) (Z = -22.38; p<0.01) and that a significantly higher proportion of households provided proxy responses in phone-based CES (51%) compared to in-person CES (21%) (Z = 20.23; p<0.01). CONCLUSIONS: The phone-based CES may be a viable option to evaluate treatment coverage but issues such as participation bias, gender inclusion, and quality of responses will need to be addressed to optimize this methodology.

Perceptions Associated with Noncompliance to Community-Wide Mass Drug Administration for Soil-Transmitted Helminths.

Mass drug administration (MDA) is a key strategy for the control of soil-transmitted helminths (STHs). Within MDA programs, poor and non-random compliance threaten successful control of STHs. A case-control study was conducted comparing perceptions among non-compliant participants with compliant participants during a community-wide MDA (cMDA) with albendazole in southern India. Common reasons cited for non-compliance were that the individual was not infected with STH (97.4%), the perception that he/she was healthy (91%), fear of side-effects (12.8%), and dislike of consuming tablets (10.3%). Noncompliance was associated with poor awareness of intestinal worms (odds ratio [OR]: 9.63, 95% CI: 2.11-43.84), the perception that cMDA was only required for those with worms (OR: 2.14, 95% CI: 1.06-4.36), and the perception that the drug is not safe during pregnancy (OR: 2.19, 95% CI: 1.18-4.07) or when on concomitant medications (OR: 3.14, 95% CI: 1.38-7.15). Understanding of perceptions driving noncompliance can provide valuable insights to optimize participation during MDA for STHs.

Costs of community-wide mass drug administration and school-based deworming for soil-transmitted helminths: evidence from a randomised controlled trial in Benin, India and Malawi.

OBJECTIVES: Current guidelines for the control of soil-transmitted helminths (STH) recommend deworming children and other high-risk groups, primarily using school-based deworming (SBD) programmes. However, targeting individuals of all ages through community-wide mass drug administration (cMDA) may interrupt STH transmission in some settings. We compared the costs of cMDA to SBD to inform decision-making about future updates to STH policy. DESIGN: We conducted activity-based microcosting of cMDA and SBD for 2 years in Benin, India and Malawi within an ongoing cMDA trial. SETTING: Field sites and collaborating research institutions. PRIMARY AND SECONDARY OUTCOMES: We calculated total financial and opportunity costs and costs per treatment administered (unit costs in 2019 USD ($)) from the service provider perspective, including costs related to community drug distributors and other volunteers. RESULTS: On average, cMDA unit costs were more expensive than SBD in India ($1.17 vs $0.72) and Malawi ($2.26 vs $1.69), and comparable in Benin ($2.45 vs $2.47). cMDA was more expensive than SBD in part because most costs (~60%) were 'supportive costs' needed to deliver treatment with high coverage, such as additional supervision and electronic data capture. A smaller fraction of cMDA costs (~30%) was routine expenditures (eg, drug distributor allowances). The remaining cMDA costs (~10%) were opportunity costs of staff and volunteer time. A larger percentage of SBD costs was opportunity costs for teachers and other government staff (between ~25% and 75%). Unit costs varied over time and were sensitive to the number of treatments administered. CONCLUSIONS: cMDA was generally more expensive than SBD. Accounting for local staff time (volunteers, teachers, health workers) in community programmes is important and drives higher cost estimates than commonly recognised in the literature. Costs may be lower outside of a trial setting, given a reduction in supportive costs used to drive higher treatment coverage and economies of scale. TRIAL REGISTRATION NUMBER: NCT03014167.

It depends on how you tell: a qualitative diagnostic analysis of the implementation climate for community-wide mass drug administration for soil-transmitted helminth.

OBJECTIVES: Current soil-transmitted helminth (STH) morbidity control guidelines primarily target deworming of preschool and school-age children. Emerging evidence suggests that community-wide mass drug administration (cMDA) may interrupt STH transmission. However, the success of such programmes depends on achieving high treatment coverage and uptake. This formative analysis was conducted to evaluate the implementation climate for cMDA and to determine barriers and facilitators to launch. SETTINGS: Prior to the launch of a cMDA trial in Benin, India and Malawi. PARTICIPANTS: Community members (adult women and men, children, and local leaders), community drug distributors (CDDs) and health facility workers. DESIGN: We conducted 48 focus group discussions (FGDs) with community members, 13 FGDs with CDDs and 5 FGDs with health facility workers in twelve randomly selected clusters across the three study countries. We used the Consolidated Framework for Implementation Research to guide the design of the interview guide and thematic analysis. RESULTS: Across all three sites, aspects of the implementation climate that were facilitators to cMDA launch included: high community member demand for cMDA, integration of cMDA into existing vaccination campaigns and/or health services, and engagement with familiar health workers. Barriers to launching cMDA included mistrust towards medical interventions, fear of side effects and limited perceived need for interrupting STH transmission. We include specific recommendations from community members regarding cMDA distribution sites, personnel requirements, delivery timing and incentives, leaders to engage and methods for mobilising participants. CONCLUSIONS: Prior to launching the cMDA programme as an alternative to school-based MDA, cMDA was found to be generally acceptable across diverse geographical and demographic settings. Community members, CDDs and health workers felt that engaging communities and tailoring programmes to the local context are critical for success. Potential barriers may be mitigated by identifying local concerns and addressing them via targeted community sensitisation prior to implementation. TRIAL REGISTRATION NUMBER: NCT03014167; Pre-results.

Impact of the COVID-19 National Lockdown on a Rural and Tribal Population of Tamil Nadu, Southern India: A Mixed-Methods Survey.

We assessed the impact of the national lockdown on a rural and tribal population in Tamil Nadu, southern India. A mixed-methods approach with a pilot-tested, semi-structured questionnaire and focus group discussions were used. The impact of the lockdown on health, finances, and livelihood was studied using descriptive statistics. Multivariable logistic regression was carried out to identify factors associated with households that borrowed loans or sold assets during the lockdown, and unemployment during the lockdown. Of the 607 rural and tribal households surveyed, households from comparatively higher socioeconomic quintiles (adjusted odds ratio [aOR], 1.84; 95% CI, 1.01-3.34), with no financial savings (aOR, 2.91; 95% CI, 1.17-7.22), and with larger families (aOR, 1.76; 95% CI, 1.22-2.53), took loans or sold assets during the lockdown. Previously employed individuals from rural households (aOR, 5.07; 95% CI, 3.30-7.78), lower socioeconomic households (aOR, 3.08; 95% CI, 1.74, 5.45), and households with no savings (aOR, 1.78; 95% CI, 1.30-2.44) became predominantly unemployed during the lockdown. Existing government schemes for the elderly, differently abled, and widows were shown to be accessible to 89% of the individuals requiring these schemes in our survey. During the focus group discussions, the limited reach of online classes for schoolchildren was noted and attributed to the lack of smartphones and poor Internet connectivity. Although the sudden, unannounced national lockdown was imposed to flatten the COVID-19 curve, aspects related to livelihood and financial security were affected for both the rural and tribal populations.

Community Drug Distributor Knowledge, Attitudes, and Motivation Surrounding Mass Drug Administration for Soil-Transmitted Helminths in India.

Background: DeWorm3 is an ongoing multi-country community-based cluster-randomized trial assessing the feasibility of interrupting transmission of soil-transmitted helminths (STH) with community-wide mass drug administration (cMDA). In Tamil Nadu, India, community drug distributors (CDDs) worked with DeWorm3 field staff to counsel community members and deliver door-to-door deworming treatment. As CDDs were likely to influence successful delivery of cMDA, we describe drivers of CDDs' knowledge, attitudes, and motivation toward delivery of cMDA. Methods: In this convergent mixed-methods study, a questionnaire on STH and cMDA was administered to 104 CDDs and 17 focus group discussions (FGDs) were conducted. Key outcomes in the quantitative and qualitative analyses included CDDs' knowledge about STH and cMDA and attitudes toward cMDA for STH. Univariate and multivariable logistic regression analyses were performed to determine the strength of associations between independent and outcome variables. The FGDs were analyzed using a priori thematic coding. Results: CDDs who completed at least secondary school education [adjusted odds ratio (aOR): 2.71, 95% CI: 1.16-6.33] and had prior experience in health programs (aOR: 2.72, 95% CI: 1.15-6.44) were more knowledgeable about STH and cMDA. CDDs belonging to the scheduled castes and scheduled tribes (aOR: 2.37, 95% CI: 1.04-5.39), and to households engaged in a skilled occupation (aOR: 2.77, 95% CI: 1.21-6.34) had a more positive attitude toward cMDA for STH. The FGDs showed that while there were myths and misconceptions about STH, many CDDs believed that the adult population in their communities were infected with STH, and that a door-to-door drug delivery strategy would be optimal to reach adults. Conclusions: Educational and socioeconomic backgrounds and experience in health programs should be considered while designing CDD trainings. Along with cMDA delivery for STH, as CDD do share community myths and misconceptions around STH, they should be proactively addressed during the CDD training to strengthen competency in counseling.

Costing interventions in the field: preliminary cost estimates and lessons learned from an evaluation of community-wide mass drug administration for elimination of soil-transmitted helminths in the DeWorm3 trial.

OBJECTIVE: To present a costing study integrated within the DeWorm3 multi-country field trial of community-wide mass drug administration (cMDA) for elimination of soil-transmitted helminths. DESIGN: Tailored data collection instruments covering resource use, expenditure and operational details were developed for each site. These were populated alongside field activities by on-site staff. Data quality control and validation processes were established. Programmed routines were used to clean, standardise and analyse data to derive costs of cMDA and supportive activities. SETTING: Field site and collaborating research institutions. PRIMARY AND SECONDARY OUTCOME MEASURES: A strategy for costing interventions in parallel with field activities was discussed. Interim estimates of cMDA costs obtained with the strategy were presented for one of the trial sites. RESULTS: The study demonstrated that it was both feasible and advantageous to collect data alongside field activities. Practical decisions on implementing the strategy and the trade-offs involved varied by site; trialists and local partners were key to tailoring data collection to the technical and operational realities in the field. The strategy capitalised on the established processes for routine financial reporting at sites, benefitted from high recall and gathered operational insight that facilitated interpretation of the estimates derived. The methodology produced granular costs that aligned with the literature and allowed exploration of relevant scenarios. In the first year of the trial, net of drugs, the incremental financial cost of extending deworming of school-aged children to the whole community in India site averaged US$1.14 (USD, 2018) per person per round. A hypothesised at-scale routine implementation scenario yielded a much lower estimate of US$0.11 per person treated per round. CONCLUSIONS: We showed that costing interventions alongside field activities offers unique opportunities for collecting rich data to inform policy toward optimising health interventions and for facilitating transfer of economic evidence from the field to the programme. TRIAL REGISTRATION NUMBER: NCT03014167; Pre-results.

A One Health Approach to Defining Animal and Human Helminth Exposure Risks in a Tribal Village in Southern India.

The high burden of soil-transmitted helminth infections has been studied in India; however, little data exist on zoonotic helminths, and on animal-associated exposure to soil-transmitted helminths. Our study took place in the Jawadhu Hills, which is a tribal region in Tamil Nadu, India. Using a One Health approach, we included animal and environmental samples and human risk factors to answer questions about the associations among infected household soil, domestic animals, and human risk factors. Helminth eggs were identified by microscopy in animal and soil samples, and a survey about risk factors was administered to the head of the household. Contact with animals was reported in 71% of households. High levels of helminth infections were found across domestic animal species, especially in goats, chickens, and dogs. Helminth eggs were recorded in 44% of household soil (n = 43/97) and separately in 88% of soil near a water source (n = 28/32). Animal contact was associated with 4.05 higher odds of having helminth eggs in the household soil (P = 0.01), and also having a water source at the household was associated with a 0.33 lower odds of having helminth eggs in the household soil (P = 0.04). Soil moisture was a mediator of this association with a significant indirect effect (P < 0.001). The proportion mediated was 0.50. While our work does not examine transmission, these results support consideration of animal-associated exposure to STH and potentially zoonotic helminths in future interventions to reduce helminth burden. Our study provides support for further investigation of the effects of animals and animal fecal matter on human health.

Gender differences in the perceived need for community-wide deworming: Formative qualitative research from the DeWorm3 study, India.

Current soil-transmitted helminth (STH) programs target morbidity control with school-based deworming. Increasing interest in steering neglected tropical disease (NTD) programmes from morbidity control towards disease elimination has prompted evaluation of strategies that may interrupt transmission. The feasibility of interrupting transmission of STH with community-wide deworming is being tested in the ongoing DeWorm3 cluster randomized trial. Gender-based perspectives about susceptibility to infection and need for treatment have been shown to influence both health-seeking behaviour and health outcomes. We carried out a qualitative study among men and women in the community to understand their knowledge, beliefs, and attitudes about STH infections and community-wide mass drug administration (cMDA). Eight semi-structured focus group discussions were conducted among men and women residing in the DeWorm3 study site in India-Vellore and Tiruvannamalai districts of Tamil Nadu. Thematic coding was used to analyse the transcripts in ATLAS.ti 8.0. Both men and women in this study demonstrated a high level of STH knowledge but some men had misconceptions that intestinal worms were beneficial. Men and women shared several similar beliefs and attitudes regarding STH treatment. Both believed that adults were likely to have STH infections and both reported that stigma prevented them from seeking treatment. Influenced by gender norms, women were more likely to associate STH infections with inadequate sanitation and hygiene, while men were more likely to believe that those engaged in agricultural work were at risk. Both genders reported a positive attitude towards cMDA for STH. Barriers to cMDA implementation differed by gender; women expressed concern regarding side-effects and drug quality while men were concerned that treatment coverage may be affected due to the absence of people during the day when the drug is distributed. Both men and women perceived the treatment of adults for STH infections to be important, however, the perceived barriers to participating in cMDA differed by gender in this community. The study identified key messages to be incorporated in communication and outreach strategies for cMDA programmes.

Development and application of an electronic treatment register: a system for enumerating populations and monitoring treatment during mass drug administration.

We developed an electronic treatment register for the DeWorm3 Project, a cluster-randomised, controlled trial in Benin, India, and Malawi testing the feasibility of interrupting transmission of soil-transmitted helminths through community-wide mass drug administration. The electronic treatment register was designed in xlsform, deployed via the SurveyCTO mobile data collection platform, and implemented on smartphones running the Android operating system. The versatile system enables collection of census and treatment status information, facilitates data aggregation and visualisation, and permits real-time feedback loops during implementation of mass drug administration. Here we describe the system's design and use within the DeWorm3 Project and key features, and by sharing the register here, we hope our readers will further explore its use within their research and disease-control activities.

Natural History of Cryptosporidiosis in a Birth Cohort in Southern India.

BACKGROUND: Cryptosporidium is a leading cause of moderate to severe childhood diarrhea in resource-poor settings. Understanding the natural history of cryptosporidiosis and the correlates of protection are essential to develop effective and sustainable approaches to disease control and prevention. METHODS: Children (N = 497) were recruited at birth in semiurban slums in Vellore, India, and followed for 3 years with twice-weekly home visits. Stool samples were collected every 2 weeks and during diarrheal episodes were tested for Cryptosporidium species by polymerase chain reaction (PCR). Serum samples obtained every 6 months were evaluated for seroconversion, defined as a 4-fold increase in immunoglobulin G directed against Cryptosporidium gp15 and/or Cp23 antigens between consecutive sera. RESULTS: Of 410 children completing follow-up, 397 (97%) acquired cryptosporidiosis by 3 years of age. PCR identified 1053 episodes of cryptosporidiosis, with an overall incidence of 0.86 infections per child-year by stool and serology. The median age for the first infection was 9 (interquartile range, 4-17) months, indicating early exposure. Although infections were mainly asymptomatic (693 [66%]), Cryptosporidium was identified in 9.4% of diarrheal episodes. The proportion of reinfected children was high (81%) and there was clustering of asymptomatic and symptomatic infections (P < .0001 for both). Protection against infection increased with the order of infection but was only 69% after 4 infections. Cryptosporidium hominis (73.3%) was the predominant Cryptosporidium species, and there was no species-specific protection. CONCLUSIONS: There is a high burden of endemic cryptosporidiosis in southern India. Clustering of infection is suggestive of host susceptibility. Multiple reinfections conferred some protection against subsequent infection.

Blastocystis Isolate B Exhibits Multiple Modes of Resistance against Antimicrobial Peptide LL-37.

Blastocystis is one of the most common eukaryotic organisms found in humans and many types of animals. Several reports have identified its role in gastrointestinal disorders, although its pathogenicity is yet to be clarified. Blastocystis is transmitted via the fecal-to-oral route and colonizes the large intestines. Epithelial cells lining the intestine secrete antimicrobial peptides (AMPs), including beta-defensins and cathelicidin, as a response to infection. This study explores the effects of host colonic antimicrobial peptides, particularly LL-37, a fragment of cathelicidin, on different Blastocystis subtypes. Blastocystis is composed of several subtypes that have genetic, metabolic, and biological differences. These subtypes also have various outcomes in terms of drug treatment and immune response. In this study, Blastocystis isolates from three different subtypes were found to induce intestinal epithelial cells to secrete LL-37. We also show that among the antimicrobial peptides tested, only LL-37 has broad activity on all the subtypes. LL-37 causes membrane disruption and causes Blastocystis to change shape. Blastocystis subtype 7 (ST7), however, showed relative resistance to LL-37. An isolate, ST7 isolate B (ST7-B), from this subtype releases proteases that can degrade the peptide. It also makes the environment acidic, which causes attenuation of LL-37 activity. The Blastocystis ST7-B isolate was also observed to have a thicker surface coat, which may protect the parasite from direct killing by LL-37. This study determined the effects of LL-37 on different Blastocystis isolates and indicates that AMPs have significant roles in Blastocystis infections.

Prevalence and clustering of soil-transmitted helminth infections in a tribal area in southern India.

OBJECTIVES: To estimate the prevalence, spatial patterns and clustering in the distribution of soil-transmitted helminth (STH) infections, and factors associated with hookworm infections in a tribal population in Tamil Nadu, India. METHODS: Cross-sectional study with one-stage cluster sampling of 22 clusters. Demographic and risk factor data and stool samples for microscopic ova/cysts examination were collected from 1237 participants. Geographical information systems mapping assessed spatial patterns of infection. RESULTS: The overall prevalence of STH was 39% (95% CI 36%­42%), with hookworm 38% (95% CI 35­41%) and Ascaris lumbricoides 1.5% (95% CI 0.8­2.2%). No Trichuris trichiura infection was detected. People involved in farming had higher odds of hookworm infection (1.68, 95% CI 1.31­2.17, P < 0.001). In the multiple logistic regression, adults (2.31, 95% CI 1.80­2.96, P < 0.001), people with pet cats (1.55, 95% CI 1.10­2.18, P = 0.011) and people who did not wash their hands with soap after defecation (1.84, 95% CI 1.27­2.67, P = 0.001) had higher odds of hookworm infection, but gender and poor usage of foot wear did not significantly increase risk. Cluster analysis, based on design effect calculation, did not show any clustering of cases among the study population; however, spatial scan statistic detected a significant cluster for hookworm infections in one village. CONCLUSION: Multiple approaches including health education, improving the existing sanitary practices and regular preventive chemotherapy are needed to control the burden of STH in similar endemic areas.

Correlation between coinfection with parasites, cytomegalovirus, and Clostridium difficile and disease severity in patients with ulcerative colitis.

A cross-sectional study was undertaken to determine whether there was any association between intestinal infection (with parasites, cytomegalovirus, or Clostridium difficile) and clinical disease severity in patients with ulcerative colitis (UC). Consecutive cases of UC were enrolled after history and clinical examination, evaluated for presence of stool parasites (routine/special stains) and C. difficile toxins A and B (CDT) in stools. Segmental biopsies at colonoscopy were assessed for cytopathic changes of cytomegalovirus (CMV) infection. Statistical analysis was done to look for associations between the presence of infection and disease severity as assessed by the Truelove-Witts criteria. Eighty-seven patients (males = 51) of mean (SD) age 40.2 (12) years were enrolled. Thirty-nine patients (44.8 %) had severe disease, 11 (12.6 %) had moderate, and 37 (42.6 %) had mild disease. Ten (11.5 %) patients had parasites detected in stool, two (2.3%) had histological evidence of CMV, and three (3.4 %) were positive for CDT. The presence of pathogens was very significantly associated with moderate/severe UC. Thirteen of 15 cases (86 %) with detectable pathogens had moderate or severe UC compared to 37 of 72 cases (51 %) without detectable pathogens (p = 0.0194). The relative risk of a UC patient with stool pathogens having severe disease was 1.686 (95 % CI 1.250 to 2.276) compared to one without stool pathogens. The presence of stool pathogens was associated with disease severity in UC.

Burden of childhood diseases and malnutrition in a semi-urban slum in southern India.

BACKGROUND: India has seen rapid unorganized urbanization in the past few decades. However, the burden of childhood diseases and malnutrition in such populations is difficult to quantify. The morbidity experience of children living in semi-urban slums of a southern Indian city is described. METHODS: A total of 176 children were recruited pre-weaning from four geographically adjacent, semi-urban slums located in the western outskirts of Vellore, Tamil Nadu for a study on water safety and enteric infections and received either bottled or municipal drinking water based on their area of residence. Children were visited weekly at home and had anthropometry measured monthly until their second birthday. RESULTS: A total of 3932 episodes of illness were recorded during the follow-up period, resulting in an incidence of 12.5 illnesses/child-year, with more illness during infancy than in the second year of life. Respiratory, mostly upper respiratory infections, and gastrointestinal illnesses were most common. Approximately one-third of children were stunted at two years of age, and two-thirds had at least one episode of growth failure during the two years of follow up. No differences in morbidity were seen between children who received bottled and municipal water. CONCLUSIONS: Our study found a high burden of childhood diseases and malnutrition among urban slum dwellers in southern India. Frequent illnesses may adversely impact children's health and development, besides placing an additional burden on families who need to seek healthcare and find resources to manage illness.

Serum IgG responses and seroconversion patterns to Cryptosporidium gp15 among children in a birth cohort in south India.

The correlates of protective immunity to cryptosporidiosis are not well understood. This study was conducted to assess the effect of maternal serum IgG against Cryptosporidium gp15 on responses to this antigen in children with (cases) and without (controls) PCR-confirmed cryptosporidial diarrhea. Maternal sera (n = 129) and sera from cases (n = 39) and controls (n = 90) collected at 3.5, 9, and 24 months of age were tested for serum IgG against Cryptosporidium gp15 by enzyme-linked immunosorbent assay (ELISA). Seroconversion patterns were evaluated by estimating probabilities of seroconversion along three time points based on the transition pathways by using a first-order Markov chain process and empirical Bayesian estimates. There was no difference in serum IgG levels or seropositivity rates to gp15 between cases and controls across all time points in children or in IgG levels to this antigen between mothers of cases and controls. The most common transition pathway can be described as a seronegative child at 3.5 months who seroconverts at 9 months and remains seropositive at 24 months. This pattern remained stable irrespective of the serological status of the mother or the case or control status of the child. Children were most likely to be exposed to Cryptosporidium for the first time between the ages of 3 and 9 months, and most of the children seroconverted by 24 months. The high degree of seroconversion among control children is suggestive of high rates of asymptomatic transmission in this region.

Systemic antibody responses to the immunodominant p23 antigen and p23 polymorphisms in children with cryptosporidiosis in Bangladesh.

Cryptosporidium is a major cause of diarrhea in children in developing countries. However, there is no vaccine available and little is known about immune responses to protective antigens. We investigated antibody responses to p23, a putative vaccine candidate, in children in Bangladesh with cryptosporidiosis and diarrhea (cases) and uninfected children with diarrhea (controls), and p23 gene polymorphisms in infecting species. Serum IgM, IgG, and IgA responses to p23 were significantly greater in cases than controls after three weeks of follow-up. Cases with acute diarrhea had significantly greater serum IgA and IgM responses than those with persistent diarrhea, which suggested an association with protection from prolonged disease. The p23 sequences were relatively conserved among infecting species and subtype families. Although most children were infected with Cryptosporidium hominis, there was a cross-reactive antibody response to C. parvum antigen. These results support further development of p23 as a vaccine candidate.