Date Published: April 05, 2018
Publisher: The American Society of Tropical Medicine and Hygiene
Author(s): Siobhan M. Mor, Luke R. Ascolillo, Ritah Nakato, Grace Ndeezi, James K. Tumwine, Alphonse Okwera, Jerlyn K. Sponseller, Saul Tzipori, Jeffrey K. Griffiths.
Respiratory cryptosporidiosis is thought to be a rare, end-stage complication of HIV. Few studies have systematically examined the frequency of such infection in adults. Sputum specimens submitted for tuberculosis (TB) testing at Mulago Hospital, Uganda, were anonymously retested for Cryptosporidium using real-time polymerase chain reaction (PCR). Visual confirmation using immunofluorescence confocal microscopy was performed for a subset of PCR-positive samples. Of 824 sputum samples tested, 24 (2.9%) were Cryptosporidium positive. Prevalence in sputum ranged between 0% and 10% in each month of the study and exceeded TB prevalence in some months. In this referral population, respiratory Cryptosporidium prevalence was lower in people with HIV (1.3% versus 4.4% without HIV, P = 0.028) and higher in those with TB (6.8% versus 2.6% without TB, P = 0.086). The weak association between respiratory Cryptosporidium infection and TB persisted after controlling for HIV (odds ratio = 3.2, 95% confidence interval: 0.9, 11.8; P = 0.080). This is the first study to document adult respiratory tract cryptosporidiosis in a referral population with presumed TB. These findings 1) confirm that Cryptosporidium respiratory infection occurs in HIV-negative and -positive adults; 2) suggest there is potential for Cryptosporidium to be disseminated or transmitted by coughing or expectoration; and 3) identify possible synergy between Cryptosporidium and TB in the respiratory tract.
Cryptosporidiosis is a common, emerging disease, unrecognized before the AIDS pandemic, and historically underappreciated as a cause of childhood diarrhea and death. Recently, the Global Enteric Multicenter Study revealed the parasite to be the second leading cause of moderate-to-severe diarrhea in infants in five of seven sites across Africa and Asia,1 with an estimated 2.9 million cases in sub-Saharan Africa alone.2 Indeed, in Uganda, we have found that 25% of children presenting with diarrhea to the national referral hospital have Cryptosporidium sp. in their stool and the 2-week case fatality rate in such children is 13%.3 Others have documented growth retardation, malnutrition, and death in children elsewhere in Africa as a result of Cryptosporidium infection.4,5 No effective therapy for cryptosporidiosis exists; nitazoxanide shortens diarrhea duration in normal hosts by 1–4 days, and is ineffective in people with HIV/AIDS.6–9 Thus, population-wide protection against this pathogen is primarily through the prevention of transmission, which is understood to occur via ingestion of parasites through direct contact with infected people or animals, or indirectly via ingestion of contaminated food and/or water.
Between April 2014 and November 2015, 824 sputum samples were obtained from anonymous, adult donors. Table 1 shows the demographic and clinical characteristics of donors. Median age of donors was 30 years (range: 18–92). Prevalence of TB and HIV (if known) among the donors was 7.2% and 36.7%, respectively. TB was not associated with HIV in this referral population (7.7% in HIV-positive donors versus 6.4% in HIV-negative donors, P = 0.632).
In our previous work, we showed that respiratory involvement occurs frequently in children with intestinal cryptosporidiosis in Uganda.19 Although there have been several historical case reports/series of respiratory Cryptosporidium infection in adults,10 no studies have systematically investigated the occurrence of respiratory cryptosporidiosis in adults in Africa or elsewhere. In the present study, we found that around 3% of adults presenting for TB testing in Uganda—10% in some months—had Cryptosporidium spp. in their sputum. The intestinal status of these anonymous, adult sputum donors was not known and therefore we are unable to comment on the frequency of respiratory involvement in adults with intestinal cryptosporidiosis. Nevertheless, the finding that a proportion of adults with presumptive TB are expectorating parasites in sputum was unanticipated. This finding is supported by the use of multiple diagnostic approaches, which included screening with a SYBR-based nested PCR protocol followed by confirmation using a probe-based assay, as well as immunofluorescence microscopy on a small number of samples.
This study is the first study to systematically investigate respiratory cryptosporidiosis in adults with suspected TB. Parasites were detected in expectorated sputum using PCR and immunofluorescence in both HIV-positive and -negative patients. A positive albeit insignificant association with TB was documented.