Transmission and the Respiratory Tract in Cryptosporidiosis
Condition: Cryptosporidiosis
MeSH terms: Cryptosporidiosis
Study type: Observational

Summary: 
      Cryptosporidium is an intestinal parasite that causes diarrhea in children and adults. In
      addition to infection of the stomach, this parasite can infect the respiratory system causing
      a cough and/or problems breathing. This study will enroll 480 children between the ages of 9
      and 36 months who come to Mulago Hospital for treatment of diarrhea. Researchers believe a
      large number of children with diarrhea and cough will have the parasite present in their
      sputum (mucus coughed up). Researchers also believe that children who have respiratory tract
      cryptosporidiosis may have a cough, increased number of breaths per minute, and/or a lower
      oxygen level. Blood, stool, saliva, and sputum samples will be collected from all children in
      the study and tested for Cryptosporidium. Children too young to provide a sputum sample will
      have a tube placed to collect a mucus sample from the lungs. Study participation may be as
      short as 4 hours or as long as 2 days depending on each child's health.
    

Detailed description: 
      Cryptosporidiosis is recognized as a major cause of diarrhea worldwide. In addition to
      infection of the gastrointestinal tract and associated fecal-oral transmission, there is
      evidence that Cryptosporidium can infect the respiratory tract. Of particular interest are
      numerous reports indicating that respiratory symptoms occur with considerable frequency in
      subjects with intestinal cryptosporidiosis although the etiology of the respiratory symptoms
      was never investigated. The association between respiratory symptoms and intestinal
      cryptosporidiosis is particularly strong in children with questionable nutritional status.
      This study will evaluate the prevalence and clinical presentation of respiratory
      cryptosporidiosis among children with diarrhea in Mulago Hospital, Kampala, Uganda. The study
      will screen approximately 1536 children aged 9-36 months who present to the Acute Care Unit
      of Mulago Hospital in Kampala, Uganda, with acute or persistent diarrhea. Based on the
      results of fecal testing, 480 children will be actively selected to undergo further sample
      collection in 2 groups. Group 1 will be comprised of children with Cryptosporidium-positive
      stools, approximately 50% of whom are expected to have cough (n=384). Group 2 will be
      comprised of children with Cryptosporidium-negative stools and cough (n=96). The primary
      objectives of the study are: to establish the prevalence of cough in children with diarrhea
      due to Cryptosporidium infection; to establish the prevalence of respiratory tract
      cryptosporidiosis in children with diarrhea due to Cryptosporidium infection; to establish
      the prevalence of respiratory tract cryptosporidiosis in children with diarrhea due to other
      causes; and to determine whether respiratory Cryptosporidium infection in children is
      associated with increased respiratory rates and decreased oxygen saturation levels. To
      address these objectives, the study will focus on whether Cryptosporidium oocysts can be
      recovered from induced sputum of subjects who have acute or persistent diarrhea and are
      concurrently experiencing a cough or unexplained tachypnea or hypoxemia. The primary clinical
      measures include: duration of diarrhea (days); presence and duration of cough (days);
      respiratory rate at presentation and if dehydrated, after rehydration; oxygen saturation (as
      measured by pulse oximetry) at presentation; and oxygen therapy requirement and oxygen
      saturation after 30 minutes of oxygen therapy if initial saturation is <92%. Primary
      parasitological measures include: presence or absence of Cryptosporidium in stool (as
      detected by modified acid fast staining and PCR); presence or absence of Cryptosporidium in
      sputum (as detected by PCR); and presence or absence of Cryptosporidium in saliva (as
      detected by PCR). Secondary clinical measures include: HIV status (determined by voluntary
      HIV testing via enzyme-linked immunosorbent assay + reverse transcriptase PCR in children
      aged less than 18 months); CD4+ counts/percentages (as measured by flow cytometry in children
      tested for HIV); concurrent respiratory infection (as determined by processing of sputum for
      routine bacterial pathogens, tuberculosis and pneumocystis jirovecii pneumonia; anemia
      (determined by hemoglobin measurement from complete blood count); and nutritional status (as
      determined from the weight-for-age score, height-for-age score, weight-for-height score, head
      circumference, and mid upper arm circumference). Secondary parasitological measurements
      include: species of Cryptosporidium in stool, in sputum, and in saliva (as determined by
      restriction fragment length polymorphism). Subject participation duration in the study is
      dependent on the health status of the child at admission and the extent of clinical care
      required. In uncomplicated cases, subject duration may be as short as 4 hours. In subjects
      requiring extensive clinical care subject duration may extend to 2 days.
    

Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Children attending the Acute Care Unit at Mulago Hospital, Kampala, Uganda
      
Keywords: cryptosporidiosis, Cryptosporidium, Uganda, diarrhea