Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger.

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.

Efficacy of halofuginone products to prevent or treat cryptosporidiosis in bovine calves: a systematic review and meta-analyses.

A prior systematic review on the efficacy of halofuginone (HFG) treatment to prevent or treat cryptosporidiosis in bovine calves was inconclusive. We undertook an updated synthesis and meta-analyses on key outcomes for the treatment of calves with HFG. Evaluated outcomes were oocyst shedding, diarrhoea, mortality and weight gain. Experiments had to describe results for same age animals in contemporary arms. Most doses were 100-150 mcg kg-1 day-1. Results were subgrouped by study design, experiments with the lowest risk of bias and lack of industry funding. Eighteen articles were found that described 25 experiments. Most evidence came from randomized controlled trials in Europe. Significantly lower incidence of oocyst shedding, diarrhoea burden and mortality was reported when treatment started before calves were 5 days old. Most studies reported on outcomes for animals up to at least 28 days old. Publication bias was possible in all outcomes and seemed especially likely for diarrhoea outcomes. Beneficial results when HFG treatment was initiated in calves older than 5 days were also found. Prophylactic treatment to prevent cryptosporidiosis is effective in preventing multiple negative outcomes and is beneficial to calf health and will result in a reduction of environmental contamination by Cryptosporidium oocysts.

Outbreak of cryptosporidiosis due to Cryptosporidium parvum subtype IIdA19G1 in neonatal calves on a dairy farm in China.

Neonatal diarrhea is one of the most important syndromes in dairy cattle. Among enteropathogens, Cryptosporidium spp. are primary causes of diarrhea, but outbreaks due to cryptosporidiosis are rarely reported in cattle. From January to April in 2016, severe diarrhea was observed in over 400 neonatal dairy calves on a large dairy farm in Jiangsu Province of East China. Approximately 360 calves died due to watery diarrhea despite antibiotic therapy. In this study, 18 fecal specimens were collected from seriously ill calves on this farm during the diarrhea outbreak, and analysed for common enteropathogens by enzymatic immunoassay (EIA). In a post-outbreak investigation, 418 and 1372 specimens collected from animals of various age groups were further analysed for rotavirus and Cryptosporidium spp. by EIA and PCR, respectively, to assess their roles in the occurrence of diarrhea on the farm. Cryptosporidium spp. were genotyped using established techniques. Initial EIA tests showed that 15/18 seriously ill calves during the outbreak were positive for Cryptosporidium parvum, while 8/18 were positive for rotavirus. The overall infection rate of Cryptosporidium in pre-weaned calves on the farm was 22.7%, with odds of the Cryptosporidium infection during the outbreak 4.4-23.5 times higher than after the outbreak. Four Cryptosporidium spp. were identified after the outbreak including C. parvum (n = 79), Cryptosporidium ryanae (n = 48), Cryptosporidium bovis (n = 31), and Cryptosporidium andersoni (n = 3), with co-infections of multiple species being detected in 34 animals. Infection with C. parvum (73/79) was found in the majority of calves aged ≤3 weeks, consistent with the age of ill calves during the outbreak. All C. parvum isolates were identified as subtype IIdA19G1. In the post-outbreak investigation, C. parvum infection was associated with the occurrence of watery diarrhea in pre-weaned calves, C. ryanae infection was associated with moderate diarrhea in both pre- and post-weaned calves, while no association was identified between rotavirus infection and the occurrence of diarrhea. Results of logistic regression analysis further suggested that C. bovis infection might also be a risk factor for moderate diarrhea in calves. Thus, we believe this is the first report of a major outbreak of severe diarrhea caused by C. parvum IIdA19G1 in dairy calves. More attention should be directed toward preventing the dissemination of this virulent subtype in China.

Risk factors for death among children 0-59 months of age with moderate-to-severe diarrhea in Manhiça district, southern Mozambique.

BACKGROUND: Despite major improvements in child survival rates, the number of deaths due to diarrhea remains unacceptably high. We aimed to describe diarrhea-associated mortality and evaluate risk factors for death among Mozambican children with moderate-to-severe diarrhea (MSD). METHODS: Between December 2007 and November 2012, children under-five with MSD were enrolled in Manhiça district, as part of the Global Enteric Multicenter study (GEMS). Clinical, epidemiological, and socio-demographic characteristics were collected. Anthropometric measurements were performed and stool samples collected upon recruitment. A follow-up visit ~ 60 days post-enrolment was conducted and verbal autopsies performed in all death cases. RESULTS: Of the 916 MSD-cases analyzed; 90% (821/916) completed 60 days follow-up and 69 patients died. The case fatality rate at follow-up was 8% (69/821), and the mortality rate 10.2 (95%CI: 7.75-13.59) deaths per 1000 persons-week at risk. Nearly half of the deaths 48% (33/69) among study participants clustered within 2 weeks of the onset of diarrhea. Typical enteropathogenic Escherichia coli (typical EPEC) and Cryptosporidium were the two pathogens associated to an increased risk of death in the univariate analysis with (HR = 4.16, p = 0.0461) and (H = 2.84, p = 0.0001) respectively. Conversely, Rotavirus infection was associated to a decreased risk of death (HR = 0.52, p = 0.0198). According to the multivariate analysis, risk factors for death included co-morbidities such as malnutrition (HR = 4.13, p <  0.0001), pneumonia/lower respiratory infection (HR = 3.51, p <  0.0001) or invasive bacterial disease (IBD) (HR = 6.80, p = 0.0009), presenting on arrival with lethargy or overt unconsciousness (HR = 1.73, p = 0.0302) or wrinkled skin (HR = 1.71, p = 0.0393), and cryptosporidium infection (HR = 2.14, p = 0.0038). When restricting the analysis to those with available HIV results (n = 191, 22% of the total study sample), HIV was shown to be a significant risk factor for death (HR = 5.05, p = 0.0009). Verbal autopsies were conducted in 100% of study deaths, and highlighted diarrhea as the main underlying cause of death 39%, (27/69); followed by HIV/AIDS related deaths 29.0% (20/69) and sepsis 11.6% (8/69). CONCLUSION: Preventive strategies targeting Cryptosporidium, malnutrition and early identification and treatment of associated co-morbidities could contribute to the prevention of the majority of diarrhea associated deaths in Mozambican children.

Molecular and histopathological features of Cryptosporidium ubiquitum infection in imported chinchillas Chinchilla lanigera in Japan.

Long-tailed chinchillas Chinchilla lanigera are popular rodent species kept both in households, where they are hand-raised as pets, and in zoological facilities. From January 2016 to February 2017, 13 juvenile chinchillas from five facilities in Japan were diagnosed with cryptosporidiosis at the animal hospital. Eight of the cases were fatal. All of the animals were imported from the Czech Republic by the same vendor. Histopathological and multilocus sequence analyses using 18S ribosomal RNA, actin, 70-kDa heat shock protein, and 60-kDa glycoprotein genes confirmed Cryptosporidium ubiquitum of subtype XIId as the etiological agent. Multilocus analysis demonstrated the presence of two new sequence types closely related to the C. ubiquitum Xlld strain isolated from a human in the USA. This study indicated that potentially zoonotic Cryptosporidium is widespread and may have caused a high number of deaths among imported juvenile chinchillas.

Report of fatal mixed infection with Cryptosporidium parvum and Giardia intestinalis in neonatal calves.

In the production and management of beef and dairy cattle, controlling diarrhea is one of the important concerns. Pathogenic agents of the disease, protozoan parasites including Cryptosporidium spp., are difficult to control, making prevention, diagnoses, and treatment of diarrhea. In the present study, we investigated a farm with a history of calf deaths over a period of 10 years in order to determine the cause of disease and to clarify the detailed distribution of the pathogens. In four examined calves that were reared in calf pens, all were positive with Cryptosporidium and/or Giardia, while the other breeding stock and adult cattle were negative. Molecular analyses revealed that the isolates from calves were C. parvum subtype IIaA15G2R1 as a zoonotic and G. intestinalis assemblage E. Other pathogenic bacteria and diarrhea-causing viruses were not detected. After treating the calf pens with boiling water and milk of lime (Ca[OH]2), oocysts of C. parvum and cysts of G. intestinalis were not found and no additional calves died. This is the first report to describe the mixed infection of both parasites in Japan.

The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS).

BACKGROUND: The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized. METHODS: Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated. FINDINGS: Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27-4.67) and 3.18 (95% CI, 1.85-4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73-2.08) and 1.36 (95% CI, 0.66-2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33-5.01) and 4.88 (95% CI, 0.82-8.92) in infants and 4.04 (95% CI, 0.56-7.51) and 4.71 (95% CI, 0.24-9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative. CONCLUSIONS: The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies.

Hematopoietic Stem Cell Transplantation for CD40 Ligand Deficiency: Single Institution Experience.

BACKGROUND: X-linked hyper-IgM syndrome (X-HIGM) due to mutations in the gene encoding CD40 ligand results in failure of Ig class switching and an increased propensity for recurrent sinopulmonary and other infections, and thus decreased life expectancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is curative, but long-term follow-up data are limited. PROCEDURES: We conducted a retrospective analysis of seven patients who have undergone allogeneic HSCT for HIGM syndrome at Duke University Medical Center. RESULTS: Median age at transplant was 5.2 years (range 0.7-19.3). None of the patients had active hepatic or pulmonary disease immediately prior to transplant, but all had a history of serious infections. Five patients received myeloablative conditioning, and two patients received reduced intensity conditioning. Graft sources included bone marrow, peripheral blood, and unrelated umbilical cord blood. Post-transplantation complications included veno-occlusive disease, hemorrhagic cystitis, adenoviremia, and cryptosporidium recurrence in one patient each. Two patients developed acute GVHD grades II-IV that resolved promptly with treatment and none developed extensive chronic GVHD. All patients are intravenous IgG-independent and 6/7 have normal antibody titers. Immunoglobulin (Ig) A levels normalized in all but one patient and T and B cell numbers and function are otherwise normal in all. All patients are alive at a median follow-up of 9.7 (range 9.7-16.1) years post-transplantation with predominantly donor chimerism and no recurrent infections. CONCLUSIONS: Allogeneic HSCT results in excellent survival and sustained immune reconstitution in patients with CD40 ligand deficiency using both myeloablative and reduced intensity conditioning approaches and various graft sources, including bone marrow, peripheral blood, and umbilical cord blood.

Cryptosporidium parvum infection and associated risk factors in dairy calves in western France.

This study was conducted to determine the prevalence and risk factors for Cryptosporidium infection in calf neonates on dairy farms in Normandy. Fecal samples were randomly collected between July 2010 and September 2011 from 968 calves (7-21 days old) on 97 farms. Up to 10 calves were selected and sampled per farm, and feces examined for oocysts by microscopy. C. parvum oocyst shedding was scored semi-quantitatively (0-5). A questionnaire about calf-level care and management was completed, and mortality rates were obtained from the French national registration database (BDNI). Bivariable and multivariable analyses of potential risk factors for C. parvum oocyst shedding were conducted using generalized estimating equation (GEE) models (family=Binomial).Overall, 402 out of 968 calves (41.5%) were positive for oocysts, and 25.1% of animals had a shedding score >2. Seven of the 97 farms (7%) were negative for oocysts in all fecal samples. At the time of collection, 375 calves (39%) had diarrhea, and its prevalence strongly correlated with the score for C. parvum oocyst shedding (p<0.0001). The mortality rate at 90 days was significantly greater for calves with high combined scores of diarrhea and shedding. Factors associated with the shedding of C. parvum were the Normande breed (odds ratio=1.49; 95% confidence interval (CI): 0.93-2.37), dispensing of colostrum using a bucket (odds ratio=1.37; 95% CI: 1.00-1.89), treatment with halofuginone (odds ratio=0.46; 95% CI: 0.19-1.15) and feeding with fermented milk (odds ratio=0.32; 95% CI: 0.17-0.63). C. parvum is widespread among calves under 21 days old in dairy herds of western France. Shedding of C. parvum is associated with a high incidence of diarrhea and increased risk of mortality in young calves. This study identified some associated calf-level factors, although further investigations are necessary to determine appropriate measures that farmers and veterinary practitioners should take to reduce the prevalence of C. parvum.

Disease burden of selected gastrointestinal pathogens in Australia, 2010.

OBJECTIVE: To estimate and compare disease burden attributable to six gastrointestinal pathogens (norovirus, rotavirus, Campylobacter, non-typhoidal Salmonella, Giardia, and Cryptosporidium) in Australia, 2010. METHODS: We estimated the number of acute gastroenteritis (AGE) cases and deaths, disability-adjusted life years (DALYs), and DALY/case for each pathogen. We included AGE cases that did not require medical care. Sequelae were included for Campylobacter (Guillain-Barré syndrome, reactive arthritis (ReA), irritable bowel syndrome (IBS)) and Salmonella (ReA, IBS). RESULTS: We estimated 16626069 AGE cases in Australia in 2010 (population 22 million). Of the pathogens studied, most AGE cases were attributed to norovirus (2180145), Campylobacter (774003), and Giardia (614740). Salmonella caused the fewest AGE cases (71255) but the most AGE deaths (90). The DALY burden was greatest for Campylobacter (18222 DALYs) and Salmonella (3856 DALYs), followed by the viral and protozoal pathogens. The average DALY/case was greatest for Salmonella (54.1 DALY/1000 cases), followed by Campylobacter (23.5 DALY/1000 cases). CONCLUSIONS: The pathogen causing the greatest disease burden varied according to the metric used, however DALYs are considered most useful given the incorporation of morbidity, mortality, and sequelae. These results can be used to prioritize public health interventions toward Salmonella and Campylobacter infections and to measure the impact of these interventions.

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 FINDINGS: We 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/SIGNIFICANCE: The 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.

An outbreak of massive mortality among farm rabbits associated with Cryptosporidium infection.

Cryptosporidium in farm rabbits is not often recognised due to a low prevalence and asymptomatic course of infection. Nonetheless, incidences of fatal diarrhoeic diseases are frequently noticed in the rabbitries. In this article, we report an outbreak where there was massive mortality among farm rabbits associated with Cryptosporidium infection. The disease was characterised by profuse diarrhoea resulting in the death of rabbits. A pooled faecal sample was screened for a presence of parasites using microscopy methods. In the tested sample no other parasites other than Cryptosporidium oocysts were found. Further identification of the parasite species was performed at a molecular level, using the 18 SSU rRNA, COWP and LIB13 PCR followed by a subtyping at the GP60 gene locus. Sequence analysis of GP60 gene fragment revealed the presence of a novel subtype VbA24 of Cryptosporidium cuniculus. In this outbreak a Cryptosporidium protozoan parasite played a major role in the etiology of the gastrointestinal disorders in rabbits resulting in massive mortality of the infected animals.

Efficacy of halofuginone lactate against experimental cryptosporidiosis in goat neonates.

Preliminary results obtained in calves, lambs and goat kids infected by Cryptosporidium sp. have indicated a partial prophylactic efficacy of halofuginone lactate when administered at 100 µg/kg body weight (BW). In this study, the efficacy of halofuginone lactate was evaluated in goat neonates experimentally inoculated with Cryptosporidium parvum oocysts per oral route. The trial consisted in 2 replicated experiments carried out successively at 2 months of interval. Twenty-two 2- to 4-day-old kids were experimentally inoculated once, 2-3 days after the arrival in premises, with 10(6)C. parvum oocysts per oral route and were allocated into 2 groups. Animals of group 1 acted as untreated control whereas animals of group 2 received halofuginone lactate for 10 days from the infection day to day 9 post-infection (DPI) at a daily oral dose rate of 100 µg/kg BW. Individual oocyst shedding was monitored by daily examination of faecal smears stained by carbol fuchsin and scored semi-quantitatively (0-5) until 19 DPI. Daily diarrhoea scores, weight gain and mortality were recorded. In the first experiment, oocyst excretion started 1 DPI in the control group, was highest on 4 DPI (mean score 3.6) and became undetectable from 16-19 DPI. In the treated group, oocyst shedding started 1 day later, showed lower scores compared to control on 4, 5, 6, 7 and 10 DPI and vanished from 16 to 19 DPI. No significant difference was seen for weight gains between groups. Five kids died in the control group compared to 1 kid in the treated group. In the second (replicated) experiment, oocyst excretion started 2 DPI in the control group, was highest on 4 DPI (mean score 4.5) and became undetectable 18 and 19 DPI. In the treated group, oocyst shedding started 2 days later, peaked on 13 DPI (mean score 2.3) and persisted until the end of the experiment. No significant difference was seen for weight gains between groups. Ten kids died in the control group compared to 3 kids in the treated group. The results demonstrated the efficacy of halofuginone lactate when given as a prophylactic treatment at 100 µg/kg BW during 10 days in reducing oocyst shedding, diarrhoea and mortality in goat kid cryptosporidiosis.

A cysteine protease inhibitor rescues mice from a lethal Cryptosporidium parvum infection.

Cryptosporidiosis, caused by the protozoan parasite Cryptosporidium parvum, can stunt infant growth and can be lethal in immunocompromised individuals. The most widely used drugs for treating cryptosporidiosis are nitazoxanide and paromomycin, although both exhibit limited efficacy. To investigate an alternative approach to therapy, we demonstrate that the clan CA cysteine protease inhibitor N-methyl piperazine-Phe-homoPhe-vinylsulfone phenyl (K11777) inhibits C. parvum growth in mammalian cell lines in a concentration-dependent manner. Further, using the C57BL/6 gamma interferon receptor knockout (IFN-γR-KO) mouse model, which is highly susceptible to C. parvum, oral or intraperitoneal treatment with K11777 for 10 days rescued mice from otherwise lethal infections. Histologic examination of untreated mice showed intestinal inflammation, villous blunting, and abundant intracellular parasite stages. In contrast, K11777-treated mice (210 mg/kg of body weight/day) showed only minimal inflammation and no epithelial changes. Three putative protease targets (termed cryptopains 1 to 3, or CpaCATL-1, -2, and -3) were identified in the C. parvum genome, but only two are transcribed in infected mammals. A homology model predicted that K11777 would bind to cryptopain 1. Recombinant enzymatically active cryptopain 1 was successfully targeted by K11777 in a competition assay with a labeled active-site-directed probe. K11777 exhibited no toxicity in vitro and in vivo, and surviving animals remained free of parasites 3 weeks after treatment. The discovery that a cysteine protease inhibitor provides potent anticryptosporidial activity in an animal model of infection encourages the investigation and development of this biocide class as a new, and urgently needed, chemotherapy for cryptosporidiosis.

A rare Cryptosporidium parvum genotype associated with infection of lambs and zoonotic transmission in Italy.

An outbreak of cryptosporidiosis occurred in a mixed sheep/cattle farm of Central Italy in October 2011. A total of 450 ovines (250 sheep and 200 lambs) and 140 bovines (130 cows and 10 calves) were housed in two separated units, at the time of the outbreak. About half of the lambs had diarrhea due to Cryptosporidium sp. with a mortality rate of 80%; calves were not infected. Genomic DNA was extracted from an archived slide and from fecal specimens, and the parasite was identified as Cryptosporidium parvum by PCR and sequence analysis at the CpA135 gene. Genotyping at the GP60 gene showed the presence of a very rare genotype, IIaA20G2R1. Shortly after the outbreak was identified, the son of the farm's owner, aged 18 months, experienced an acute gastroenteritis and was hospitalized due to recurrent episodes of diarrhea, fever, vomiting and lack of appetite. The feces tested negative for bacteria and viruses, whereas cryptosporidiosis was diagnosed by microscopy and an immunochromatographic test. Molecular typing identified the C. parvum genotype IIaA20G2R1 in the feces of the child. This is the first case of transmission of cryptosporidiosis in Italy involving lambs as source of oocysts infectious to humans.

Antibiotics for the treatment of Cholera, Shigella and Cryptosporidium in children.

BACKGROUND: Diarrhea is a major contributor to the burden of morbidity and mortality in children; it accounts for a median of 11% of all deaths among children aged less than 5 years, amounting to approximately 0.8 million deaths per year. Currently there is a dearth of literature exploring the effectiveness of antibiotics for diarrhea due to Cholera, Shigella and cryptosporidiosis in children. METHODS: We reviewed the literature reporting the effect of antibiotics for the treatment of diarrhea due to Cholera, Shigella and Cryptosporidium in children under five years. We used a standardized abstraction and grading format and performed meta-analyses to determine the effect of the treatment with various antibiotics on mortality and rates of clinical and bacteriological/parasitological failure. The CHERG Standard Rules were applied to determine the final effect of treatment with antibiotics on diarrhea morbidity and mortality. RESULTS: For Cholera; the evidence was weak to recommend any effect on mortality. For Shigella; there was no data on mortality; either all-cause or cause specific, hence we used clinical failure rates as a proxy for Shigella deaths and propose that treatment of Shigella dysentery with antibiotics can result in a 82% reduction in diarrhea mortality due to Shigella. For cryptosporidiosis; there was data on all-cause mortality but the evidence was weak hence we used clinical failure rates as a proxy for mortality to estimate that antimicrobial treatment of diarrhea due to cryptosporidiosis can result in a 54% reduction in mortality. CONCLUSIONS: There is evidence to recommend antibiotic use for reduction of morbidity and mortality due to Cholera, Shigella and Cryptosporidium. We recommend that more clinical trials should be conducted to evaluate the efficacy and safety of first- and second- line drugs currently in use for treatment for diarrhea and dysentery in both developing and developed countries.

Quantitative health risk assessment of Cryptosporidium in rivers of southern China based on continuous monitoring.

The concentrations of Cryptosporidium in the source water of several cities of Zhejiang Province, China were determined to be in the range of 0-17 oocysts/10 L in the rainy season in 2008, with a mean value of 7 oocysts/10 L. Based on the investigation data, comprehensive risk assessment of Cryptosporidium infection was performed by considering different water intake routes as well as water consumption. Intakes of unboiled tapwater (including drinking and tooth-brushing and food and dish washing) and source water (through swimming in rivers) were estimated to be 2.59-25.9 and 0.32-0.74 L/year-person, respectively. The mortality due to Cryptosporidium infection for people in this region, excluding HIV-infected patients, was calculated as 0-0.0146 per 10(5) persons using a conditional probability formula. Disability-adjusted life years (DALYs) were used to quantify the risk of Cryptosporidium infection, for which uncertainty was analyzed. For people who consumed conventionally treated water, the DALYs due to Cryptosporidium infection were 6.51 per 10(5) (95% CI: 2.16 × 10(-5)-22.35 × 10(-5)) persons, which were higher than a risk judged acceptable by some (1.97 × 10(-5) DALYs per year), and the risk for those consuming ozone-treated water became 0.0689 × 10(-5) DALYs per year. The major risk of infection resulted from swimming in the river. This study provides a method to establish the risk of Cryptosporidium infection and optimize the scheme for reducing the risk effectively, which is useful for the modification of water quality standards based on cost utility analysis given use of DALYs.