Cryptosporidial Diarrhea Research Articles

Clinico-Epidemiological Profile and Utility of Diagnostic Techniques in Immunocompetent Children with Cryptosporidium Diarrhoea

Purpose: To assess the Clinical and Epidemiological profile of children 6 months to 5 years having Cryptosporidium diarrhoea and to compare the diagnostic accuracy of rapid diagnostic test (RDT) against modified acid-fast stain technique to detect Cryptosporidium in stool. Materials and Methods: Details of demography, presenting complaints, and detailed examination of children presenting with acute or persistent diarrhoea were recorded in a predesigned proforma. Two Stool samples were collected and examined same day by rapid antigen test and microscopy for presence of antigen or oocyst of cryptosporidium. Results: Out of the total of 280 samples tested, 40 (14.3%) samples were positive for Cryptosporidium. The prevalence of Cryptosporidium in children presenting with diarrhoea in our study came out to be 14.3%. Fever, vomiting and pain abdomen were the most common presenting complaints. Epidemiological factors like providing clean water, proper feeding and hygiene, and avoidance of overcrowding can help in reducing the burden of Cryptosporidium diarrhoea. Persistent diarrhoea was more common among cryptosporidium positive cases. Rapid detection kits enhance the detection rate and are sensitive as well as specific. It could be utilised as an aid in diagnosis of Cryptosporidium diarrhoea. Conclusion: The study shows that cryptosporidial diarrhoea is not uncommon in immunocompetent children. Improvement in personal hygiene, feeding practices and access to safe and potable water can help in reducing burden of this disease. Antigen detection kits aid in early diagnosis. Keywords: Paediatric cryptosporidiosis, Persistent diarrhoea, Sanitation, RDT in diarrhoea, Abdominal pain

Toll-Like Receptors and Mannose Binding Lectin Gene Polymorphisms Associated with Cryptosporidial Diarrhea in Children in Southern India.

ABSTRACT.In low-resource settings, Cryptosporidium spp. is a common cause of diarrheal disease in children under the age of 3 years. In addition to diarrhea, these children also experience subclinical episodes that have been shown to affect growth and cognitive function. In this study, we screened polymorphisms in the promoter and exon1 regions of the mannose binding lectin 2 (MBL2) gene, as well as single nucleotide polymorphisms (SNPs) described in toll-like receptors (TLR) TLR1, TLR2, TLR4, and TLR9 and TIR domain-containing adaptor protein (TIRAP) genes among children with cryptosporidial diarrhea (cases) and children who only experienced asymptomatic (subclinical) cryptosporidiosis (controls). Among the polymorphisms screened, the variant allele B at codon 54 (rs1800450) of the MBL2 gene was associated with susceptibility to cryptosporidial diarrhea (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.1–4.5). When plasma MBL levels were compared, 72% of cases were found to be deficient compared with 32% among controls (OR = 5.09). Among TLR polymorphisms screened, multivariate analysis showed that heterozygous genotypes of TLR4 896A/G (rs4986790, OR = 0.33, 95% CI: 0.11–0.98) and TIRAP 539 C/T (rs8177374, OR = 0.19, 95% CI: 0.06–0.64) SNPs were associated with protection from cryptosporidial diarrhea. Although not statistically significant, these findings suggest that polymorphisms of MBL2 and TLR genes influence susceptibility to symptomatic cryptosporidial diarrhea even in settings with high exposure levels. Further studies to validate these findings in a larger cohort and to understand the role of these polymorphisms in mediating innate and adaptive immune responses to cryptosporidial infection are necessary.

Delayed Time to Cryptosporidiosis in Bangladeshi Children is Associated with Greater Fecal IgA against Two Sporozoite-Expressed Antigens.

.Cryptosporidiosis is common in early childhood, and both diarrheal and subclinical infections are associated with adverse developmental outcomes. Improved therapeutic medications may help reduce the burden of cryptosporidial diarrhea; however, an effective vaccine would be better able to prevent the detrimental impact of both diarrheal and subclinical disease. A more complete understanding of naturally occurring immunity may further inform strategies to develop an effective vaccine. In this prospective cohort study of Bangladeshi children, greater fecal IgA at 12 months, but not plasma IgG, directed against two sporozoite-expressed, immunodominant and vaccine candidate antigens was associated with delayed time to subsequent cryptosporidiosis to 3 years of life. These findings extend prior work and further support the role of mucosal antibody responses in naturally developing protective immunity to Cryptosporidium.

Conducting clinical trials in sub-Saharan Africa: challenges and lessons learned from the Malawi Cryptosporidium study

BackgroundAn effective drug to treat cryptosporidial diarrhea in HIV-infected individuals is a global health priority. Promising drugs need to be evaluated in endemic areas which may be challenged by both lack of resources and experience to conduct International Committee of Harmonisation-Good Clinical Practice (ICH-GCP)-compliant clinical trials.MethodsWe present the challenges and lessons learned in implementing a phase 2A, randomized, double-blind, placebo-controlled trial of clofazimine, in treatment of cryptosporidiosis among HIV-infected adults at a single site in Malawi.ResultsPrimary challenges are grouped under study initiation, study population, study implementation, and cultural issues. The lessons learned primarily deal with regulatory system and operational barriers, and recommendations can be applied to other human experimental trials in low- and middle-income countries, specifically in sub-Saharan Africa.ConclusionThis study demonstrated that initiating and implementing human experimental trials in sub-Saharan Africa can be challenging. However, solutions exist and successful execution requires careful planning, ongoing evaluation, responsiveness to new developments, and oversight of all trial operations.

Evaluating the safety, tolerability, pharmacokinetics and efficacy of clofazimine in cryptosporidiosis (CRYPTOFAZ): study protocol for a randomized controlled trial

BackgroundCryptosporidium infection and diarrhea (cryptosporidiosis) is a life-threatening infection in persons with HIV and also in children of 6–18 months of age in the developing world. To date, only nitazoxanide is licensed for treatment of cryptosporidiosis, and only in persons after the first year of life and with healthy immune systems. Clofazimine (CFZ: Lamprene®), an established drug that has been used for leprosy for more than 50 years, recently has been described as effective against Cryptosporidium in vitro and in mouse infections. The efficacy and pharmacokinetics of CFZ in vivo, in HIV-infected patients with cryptosporidial diarrhea are not known.MethodsCRYPTOFAZ includes a randomized, double-blind, placebo-controlled study of the safety, tolerability and Cryptosporidium inhibitory activity of orally administered CFZ in subjects with HIV infection and chronic diarrhea with Cryptosporidium. An additional open label aspect of the study will compare the pharmacokinetics (PK) of orally administered CFZ in HIV-infected individuals with and without Cryptosporidium-associated diarrhea. The study will recruit a total of 66 subjects. Study participants will be given either CFZ or a placebo for 5 days while in hospital and will be followed up after discharge. Cryptosporidium will be diagnosed by quantitative PCR as the definitive test and by stool ELISA, which will also be used to quantify the shedding of Cryptosporidium in stool. PK will be studied on plasma and stool samples. Primary endpoints include reduction in the number of Cryptosporidium shed in stools over a 5-day period and compared to placebo recipients and the PK of CFZ in plasma assessed by area under the curve, peak plasma concentration, and half-life (T ½) determined after the last dose.DiscussionThis study provides an opportunity to explore a possible treatment option for HIV-infected patients with cryptosporidial diarrhea, who, as of now in Malawi and most of sub-Saharan Africa, do not have a definitive treatment apart from supportive care. The strength of this study lies in it being a randomized, double-blind, placebo-controlled trial. If shown to be effective and safe, the findings will also lay a foundation for a future study of the use of CFZ in children 6–18 months of age.Trial registrationClinicalTrials.gov, NCT03341767. Registered on 14 November 2017.

Treatment interventions for diarrhoea in HIV-infected and HIV-exposed children: a systematic review.

IntroductionSeventy percent of an estimated 10 million children less than five years of age in developing countries die each year of acute respiratory infections, diarrhoea, measles, malaria, malnutrition or a combination of these conditions. Children living with Human immunodeficiency virus (HIV) are at risk of diarrhoea because of drug interactions with antiretroviral therapy and bottle feeding. This may be aggravated by malnutrition and other infectious diseases which are frequent in children living with HIV. Objective: to evaluate treatment interventions for diarrhoea in HIV infected and exposed children.MethodsA comprehensive search was conducted on 02 June 2016 to identify relevant studies for inclusion. We included randomised controlled trials of HIV infected or exposed children under 15 years of age with diarrhoea. Two authors independently selected studies for inclusion, assessed risk of bias (RoB) and extracted data using a pre-designed data extraction form.ResultsWe included two studies (Amadi 2002 and Mda 2010) that each enrolled 50 participants. The RoB was assessed as low-risk for both included studies. There was no difference in clinical cure and all-cause mortality between nitazoxanide and placebo for cryptosporidial diarrhoea in Amadi 2002. In Mda 2010, there was a reduction in duration of hospitalisation in the micronutrient supplement group (P < 0.005) although there was no difference in all-cause mortality.ConclusionThere is low certainty evidence on the effectiveness of nitazoxanide for treating cryptosporidial diarrhoea and micronutrient supplementation in children with diarrhoea. Adequately powered trials are needed to assess micronutrients and nitazoxanide, as well as other interventions, for diarrhoea in HIV-infected and-exposed children.

Cryptosporidiosis in children in the Indian subcontinent.

Cryptosporidiosis is a leading cause of diarrheal disease among children under two in developing countries. Previous estimates have shown a high burden of cryptosporidial diarrhea in children from Sub-Saharan Africa and South Asia. Asymptomatic cryptosporidial infections which go undetected and untreated have been shown to result in significant malnutrition. In this review, we carried out a literature search of studies published on cryptosporidiosis in children in the Indian subcontinent from 1983 to 2016. Of the 154 publications identified, 54 were included for final analysis with both hospital-based and community-based studies. There were wide variations in reported prevalence rates from hospital studies and highlight the need to be carry out these studies with uniform sampling and molecular tools for detection, especially in countries with a dearth of information. Community-based studies, however, showed similarities in spite of differences in when (the late 1990s up until recently) and where (South India or Bangladesh) they were conducted. When more sensitive detection methods were used, cryptosporidial diarrhea accounted for 7%–9% of all diarrhea episodes and 20%–30% of children in these cohorts experienced at least one cryptosporidial diarrheal episode. High rates of asymptomatic infections with increased detection by serology and multiple infections (symptomatic and asymptomatic) were also documented in all cohorts. This overview brings to light the high burden of disease associated with cryptosporidiosis in children in the subcontinent and the gaps in knowledge to be addressed.

Cryptosporidial Diarrhoea in Children at a Paediatric Hospital in Accra, Ghana

Background: Diarrhoeal diseases are common among children in developing countries, and are caused by several aetiological agents including Cryptosporidium sp. Several species of this parasite exist which may belong to either anthroponotic or zoonotic forms. With recent application of molecular tools, species involved in human transmission in any locality and sources of infection can now be determined. Aim: We screened children with acute diarrhoea at a paediatric hospital in Accra, Ghana for enteric parasites to determine frequency of cryptosporidial diarrhoea. Cryptosporidium isolates were then characterized by molecular methods to determine the genetic species in transmission. Methodology: A total of 365 diarrhoeic children of age ≤ 5 years were used in this cross-sectional study. Stool samples were collected and tested for enteric parasites by microscopy and ELISA. Cryptosporidium isolates were subsequently genotyped by PCR-RFLP and confirmed by sequencing of the 18S rRNA gene. Demographic and clinical data were obtained by a structured questionnaire and data analysed for possible association with cryptosporidial diarrhoea. Results: Enteric parasites detected were Cryptosporidium sp. (22.2%), G. lamblia (5.8%) and E. histolytica (0.8%). Neither gender nor breastfeeding habits, presence of domestic animals, source of children’s food, seasons (dry or rainy) appeared to be associated with infection of Cryptosporidium sp. However, age of children, source of drinking water, and education level of mother seems to have association with infection of the parasite. Genotyping results show that C. parvum is the only species involved in transmission. Conclusion: Cryptosporidium parvum is the commonest enteric parasite causing diarrhoea among children with acute diarrhoea. Children ≤ 3 years and those who drank sachet water were most affected. A carefully planned health education among illiterate mothers and improved sanitary conditions could reduce rate of infections. Further sub-genotyping of C. parvum is needed to determine whether source of infection is zoonotic or anthroponotic.

Burden of diarrhea, hospitalization and mortality due to cryptosporidial infections in Indian children.

Background Cryptosporidium spp. is a common, but under-reported cause of childhood diarrhea throughout the world, especially in developing countries. A comprehensive estimate of the burden of cryptosporidiosis in resource-poor settings is not available.Methodology/Principal FindingsWe used published and unpublished studies to estimate the burden of diarrhea, hospitalization and mortality due to cryptosporidial infections in Indian children. Our estimates suggest that annually, one in every 6–11 children <2 years of age will have an episode of cryptosporidial diarrhea, 1 in every 169–633 children will be hospitalized and 1 in every 2890–7247 children will die due to cryptosporidiosis. Since there are approximately 42 million children <2 years of age in India, it is estimated that Cryptosporidium results in 3.9–7.1 million diarrheal episodes, 66.4–249.0 thousand hospitalizations, and 5.8–14.6 thousand deaths each year.Conclusions/SignificanceThe findings of this study suggest a high burden of cryptosporidiosis among children <2 years of age in India and makes a compelling case for further research on transmission and prevention modalities of Cryptosporidium spp. in India and other developing countries.

The evolution of respiratory Cryptosporidiosis: evidence for transmission by inhalation.

The protozoan parasite Cryptosporidium infects all major vertebrate groups and causes significant diarrhea in humans, with a spectrum of diseases ranging from asymptomatic to life-threatening. Children and immunodeficient individuals are disproportionately affected, especially in developing countries, where cryptosporidiosis contributes substantially to morbidity and mortality in preschool-age children. Despite the enormous disease burden from cryptosporidiosis, no antiprotozoal agent or vaccine exists for effective treatment or prevention. Cryptosporidiosis involving the respiratory tract has been described for avian species and mammals, including immunocompromised humans. Recent evidence indicates that respiratory cryptosporidiosis may occur commonly in immunocompetent children with cryptosporidial diarrhea and unexplained cough. Findings from animal models, human case reports, and a few epidemiological studies suggest that Cryptosporidium may be transmitted via respiratory secretions, in addition to the more recognized fecal-oral route. It is postulated that transmission of Cryptosporidium oocysts may occur by inhalation of aerosolized droplets or by contact with fomites contaminated by coughing. Delineating the role of the respiratory tract in disease transmission may provide necessary evidence to establish further guidelines for prevention of cryptosporidiosis.

Immune Response and Intestinal Permeability in Children With Acute Gastroenteritis Treated With Lactobacillus rhamnosus GG: A Randomized, Double-Blind, Placebo-Controlled Trial

Probiotics have a possible role in the treatment of pediatric acute gastroenteritis. We report the effect of the probiotic Lactobacillus rhamnosus GG (LGG) on intestinal function, immune response, and clinical outcomes in Indian children with cryptosporidial or rotavirus diarrhea. Children with gastroenteritis aged 6 months to 5 years, testing positive for either rotavirus or Cryptosporidium species in stool (coinfections were excluded), were randomized to LGG (ATCC 53103) or placebo, once daily for 4 weeks. Baseline demographic and clinical details were obtained. Sera were tested for immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to Cryptosporidium and rotavirus, and the lactulose to mannitol ratio for intestinal permeability was determined at baseline and at the end of follow-up. Of the 124 children enrolled, 82 and 42 had rotavirus and cryptosporidial diarrhea, respectively. Median diarrheal duration was 4 days; one-third of the children had severe diarrhea. Baseline and clinical parameters were comparable between children receiving LGG and placebo. At the end of follow-up, fewer children with rotavirus diarrhea on LGG had repeated diarrheal episodes (25% vs 46%; P = .048) and impaired intestinal function (48% vs 72%; P = .027). Significant increase in IgG levels postintervention (456 vs 2215 EU; P = .003) was observed in children with rotavirus diarrhea receiving LGG. Among children with cryptosporidial diarrhea, those receiving LGG showed significant improvement in intestinal permeability. LGG has a positive immunomodulatory effect and may be useful in decreasing repeated episodes of rotavirus diarrhea. Improvement in intestinal function in children with rotavirus and cryptosporidial gastroenteritis emphasizes the role of probiotics in treating intestinal impairment after infection. CTRI/2010/091/000339.

Recent trends in the spectrum of opportunistic infections in human immunodeficiency virus infected individuals on antiretroviral therapy in South India.

Background:Opportunistic infections (OI) are the major cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals. The pattern of OIs differs widely, hence it is necessary to correlate spectrum of OIs and CD4 counts among HIV infected individuals in specific localities.Materials and Methods:The present study describes the clinical and laboratory profiles of different OIs among 55 HIV seropositive patients. CD4 count was estimated and antiretroviral therapy (ART) was started in 27 patients as per National Acquired Immunodeficiency Syndrome Control Organization guidelines. These 27 patients were classified into stage 1, stage 2 and stage 3 based on CD4 counts of >500 cells/μl, 200-499 cells/μl and <200 cells/μl respectively. The OIs presented by respective groups were documented.Results:Pulmonary tuberculosis was found to be the most common OI constituting 43.6% of all cases followed by candidiasis (30.9%), cryptosporidial diarrhea (21.8%), herpes zoster (16.3%), cryptococcal meningitis (3.63%), Pneumocystis jirovecii pneumonia (1.81%), and other miscellaneous infections (23.6%). Only 1 patient was found in stage I while 13 patients each were grouped in stage II or stage III. The mean CD4 count in our study population who were on ART was 230 ± 150 cells/µl.Conclusion:The pattern of OIs among our study group did not differ significantly from patients not receiving ART. The effect of ART on CD4 count differs from patient to patient based on the degree of depletion of CD4 count before the initiation of ART, drug adherence, concomitant OIs and their treatment.

Cryptosporidial diarrhea in a patient of all-trans-retinoic-acid syndrome treated successfully with azithromycin

Cryptosporidial diarrhea in a patient of all-trans-retinoic-acid syndrome treated successfully with azithromycin

Prevalence of Cryptosporidium infection among livestock and humans in contact with livestock in Hamadan district, Iran, 2012.

Cryptosporidium is a protozoan parasite causes cryptosporidial diarrhea, which is typically a short-lasting benign infection, but can become severe and non-resolving in immunocompromised individuals. The aim of the present study was to determinate the prevalence of Cryptosporidium infection in livestock and humans that were in contact with livestock in Hamadan district, Iran. In this cross sectional study a total of 660 fecal specimens were collected; 228, 195 and 237 from humans, whom raising livestock, their calves and lambs/goats, respectively in spring 2012. Samples were concentrated by formalin-ether concentration technique and examined using cold modified Ziehl-Neelsen staining method. Two (0.87%) out of 228, 25 (12.8%) out of 195 and 6 (2.5%) out of 237 fecal samples of humans, calves and lambs/goats were positive for Cryptosporidium oocysts, respectively. There was no significant relationship between the infection to Cryptosporidium and demographic variables of humans. However, Cryptosporidium infection rate was higher in diarrheic calves (OR=3.81; 95% CI: 1.30, 11.21; P=0.010). Despite studies conducted in some regions of Iran that resulted in a relatively high rate of infection in humans in contact with livestock, our results showed low prevalence and low carrier status in the asymptomatic persons in Hamadan region. Because the infection in calves and lambs/goats was relatively high, these animals could be probable reservoir of infection for humans in this area.

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.

Analysis of human immune responses in quasi-experimental settings: tutorial in biostatistics.

BackgroundHuman immunology is a growing field of research in which experimental, clinical, and analytical methods of many life science disciplines are utilized. Classic epidemiological study designs, including observational longitudinal birth cohort studies, offer strong potential for gaining new knowledge and insights into immune response to pathogens in humans. However, rigorous discussion of methodological issues related to designs and statistical analysis that are appropriate for longitudinal studies is lacking.MethodsIn this communication we address key questions of quality and validity of traditional and recently developed statistical tools applied to measures of immune responses. For this purpose we use data on humoral immune response (IR) associated with the first cryptosporidial diarrhea in a birth cohort of children residing in an urban slum in south India. The main objective is to detect the difference and derive inferences for a change in IR measured at two time points, before (pre) and after (post) an event of interest. We illustrate the use and interpretation of analytical and data visualization techniques including generalized linear and additive models, data-driven smoothing, and combinations of box-, scatter-, and needle-plots.ResultsWe provide step-by-step instructions for conducting a thorough and relatively simple analytical investigation, describe the challenges and pitfalls, and offer practical solutions for comprehensive examination of data. We illustrate how the assumption of time irrelevance can be handled in a study with a pre-post design. We demonstrate how one can study the dynamics of IR in humans by considering the timing of response following an event of interest and seasonal fluctuation of exposure by proper alignment of time of measurements. This alignment of calendar time of measurements and a child's age at the event of interest allows us to explore interactions between IR, seasonal exposures and age at first infection.ConclusionsThe use of traditional statistical techniques to analyze immunological data derived from observational human studies can result in loss of important information. Detailed analysis using well-tailored techniques allows the depiction of new features of immune response to a pathogen in longitudinal studies in humans. The proposed staged approach has prominent implications for future study designs and analyses.

Acute Cryptosporidiosis Following Exposure to Hydrocarbon Containing Compounds

Hydrocarbon poisoning may result from ingestion or inhalation and can provoke direct or indirect damage which may influence infectious diseases by altering natural resistance. Poisoning is a general term and is defined as the potential of a chemical substance in causing adverse effects on the body. Gastrointestinal manifestations, aspirated pneumonitis, symptoms of Central Nervous System (CNS) impairment, and hypoxia are frequent findings. Further, exposure to chemical substances has the potential in weakening the individual’s immunity to infections produced by bacteria, fungi, parasites and viruses. Present case report highlights cryptosporidial diarrhea in a patient with hydrocarbon poisoning.

Serum Antibody Responses to Polymorphic Cryptosporidium Mucin Antigen in Bangladeshi Children with Cryptosporidiosis

Cryptosporidium is a significant cause of diarrheal disease in children in developing countries. The sporozoite antigen Muc4 is important for infection of host cells, and could be a candidate vaccine antigen. However, this antigen is polymorphic between Cryptosporidium hominis and C. parvum. We investigated antibody responses to C. hominis Muc4 and C. parvum Muc4 antigen in children in Bangladesh infected with C. hominis. Antibody responses were compared between children with cryptosporidial diarrhea (cases) and uninfected children with diarrhea (controls). There was a significant IgM response to Muc4 from both species in cases compared with controls, which increased over time, and was higher in children with persistent diarrhea. Despite sequence polymorphisms, antibody responses to C. hominis Muc4 and C. parvum Muc4 were significantly correlated. These results suggest that the human antibody response to Muc4 is cross-reactive between species, but in young children does not mature to an IgG response within the period observed in this study.

Effect of cryptosporidial and giardial diarrhoea on social maturity, intelligence and physical growth in children in a semi-urban slum in south India

Early childhood diarrhoea is a major cause of infant morbidity and mortality in developing countries. Recurrent and persistent diarrhoea affect growth and cognition in children as young as 6 years. To evaluate the effect of early childhood cryptosporidial and giardial diarrhoea on growth and development in children in a semi-urban slum in India. This is the first report of such assessment at 3 years of age. This study was undertaken on 116 children who were part of an ongoing birth cohort study (n=452) of rotaviral and cryptosporidial diarrhoea between June and December 2005. Social quotients (SQ) assessed by the Vineland Social Maturity Scale, intelligence quotients (IQ) assessed by the Seguin Form Board Test, physical growth parameters and sociodemographic data in 84 children with a history of cryptosporidial or giardial diarrhoea were compared with those of 32 without diarrhoea. Children with a past history of giardial diarrhoea showed a trend towards lower SQ (p=0.09) and had significantly lower IQ (p=0.04) and increased wasting (p=0.04). Cryptosporidial diarrhoea was not associated with poor IQ, SQ or physical growth. This study demonstrates the long-term effect of protozoan diarrhoea, especially that caused by giardia, on both intelligence and physical growth in Indian children as early as 3 years of age and re-inforces the need for early detection and prevention of early childhood protozoan diarrhoea.

Serum IgG Response to Cryptosporidium Immunodominant Antigen gp15 and Polymorphic Antigen gp40 in Children with Cryptosporidiosis in South India

The surface-associated glycopeptides gp40, one of the most polymorphic Cryptosporidium antigens, and gp15, one of the most immunodominant Cryptosporidium antigens, are putative vaccine candidates because they mediate infection in vitro and induce immune responses in vivo. We evaluated antibody responses to these antigens before and after the first episode of symptomatic cryptosporidiosis in 51 children from a birth cohort study in an area in South India where Cryptosporidium is endemic and a major cause of parasitic diarrhea. IgG levels to gp15 and to homotypic and heterotypic gp40 antigens were measured in pre- and postdiarrheal sera by enzyme-linked immunosorbent assay (ELISA). There was a significant IgG response to gp15 (P < 0.001) following the first episode of cryptosporidial diarrhea. Using a general additive model, we determined the estimated time of the peak IgG response to gp15 to be 9.3 weeks (confidence interval, 5.2 to 13.4) following the diarrheal episode. In a subset of 30 children infected with Cryptosporidium hominis subtype Ia, there was a significant difference in IgG responses to homotypic C. hominis Ia and to heterotypic Cryptosporidium parvum II gp40 antigens (P = 0.035). However, there was also a significant correlation (P = 0.001) in the responses to both antigens in individual children, suggesting that while responses are in part subtype specific, there is significant cross-reactivity to both antigens. This is the first report of the characterization of immune responses to cryptosporidiosis in Indian children and the first study to investigate human immune responses to the polymorphic gp40 antigen. However, further studies are needed to determine whether immune responses to these antigens are protective against subsequent infections.