Infectious Disease Alert Updates
By Carol A. Kemper, MD, FACP
Diagnostic Puzzle? Solved by The New York Times
SOURCE: Donald G McNeil, Jr. Fighting hepatitis by slashing drug price, in lab size of Egypt. The New York Times, Dec. 16, 2015, A1; Progress toward prevention and control of hepatitis C virus infection — Egypt, 2001-2012. MMWR 2012;61:545-549.
A fascinating consult crossed my path a few weeks ago. A 70-year-old Egyptian man was referred by Oncology for hepatic microcalcifications to rule out schistosomiasis or granulomatous infection. He was to receive Rituxan and high-dose corticosteroids for lymphoplasmocytic lymphoma. Schistosoma hematobium and mansoni are both endemic in Egypt, and it has been argued whether the building of the Aswan Dam in the 1960s exacerbated the problem.
The patient was born in Cairo, came from an educated, middle-class family, and immigrated to the United States about 15 years ago. He was on the rowing team in high school, and practiced frequently on the Nile, although he knew to avoid the shallow areas. He was diagnosed with prostate cancer in 2008 and received high-dose radiation therapy and adjuvant hormonal therapy. Small foci of slowly progressive hepatic microcalcifications were observed on serial CT scans from 2008 to 2015, although there was no evidence of calcium deposition in the spleen, lymph nodes, or lung. Blood and urine studies for Schistosoma mansoni, tuberculosis, coccidioidomycosis, histoplasmosis, cystercercosis, and strongyloides were all negative. But he was positive for HBV-core IgG antibody, negative for HBV surface Ag and core IgM, and HBV DNA was undetectable; and his HCV Ab was positive. Further studies demonstrated HCV genotype 4 with a viral load of approximately 600,000. His liver function studies had consistently been normal for years. The patient had no apparent risk factors for HBV or HCV infection, and he merely shrugged when I asked the usual questions, stating that “everybody” in Egypt has hepatitis. Pending further laboratory results, I imagined that micronodular cirrhosis from his HCV was the most likely explanation for his microcalcifications.
What was the answer to this case?
Before I had a chance to investigate further, The New York Times lead article the next morning provided the answer. Indirectly, schistosomiasis was the culprit but not the cause of his problem. Egypt has the highest burden of HCV infection in the world, with seroprevalence studies demonstrating that 15% of the population has HCV antibody, and 10% are actively infected. This amounts to ~6 million Egyptians with active HCV infection. Ironically, this epidemic is largely owing to a mass campaign to control schistosomiasis in Egypt from 1960-1980 using parenteral antischistosomal therapy (e.g., praziquantal). The patient confirmed that he and his school buddies were lined up and sequentially injected using non-sterile syringes. The boys were more frequently “vaccinated” than girls, because the boys were more athletic and more likely to get infected. And, indeed, seroprevalence studies in Egypt confirm that 12% of men and 8% of women are HCV-infected. Poor infection control practices, unsafe medical injections, and bad dental practices only exacerbated the problem for the next few decades.
As a response to this epidemic, National Egyptian Guidelines for the prevention of transmission of HCV and Infection Control practices were published in 2003; a National Committee for the control of viral hepatitis was established in 2006; and a National Strategy for Control for Viral Hepatitis developed in 2008. This involves a complex treatment campaign, costing approximately $200 million per year, about 40% of which is supported by public health dollars (about 20% of the Egyptian healthcare budget). The government’s goal is to treat 300,000 cases of HCV infection per year, driving down the prevalence of HCV infection to less than 2% of the population by 2025.
Licensing of technologies for the manufacture of antiviral medications has been a key part of the strategy. Gilead Sciences, based in California, licenses the rights to manufacture and market sofosbuvir (Solvaldi) to 11 Indian companies and two Egyptian companies, in exchange for 7% of the royalties. There were plans to begin manufacturing Harvoni, a combination pill containing sofosbuvir and ledipasvir, in December 2015. The result is that sofosbuvir costs about $10 per day per pill for a 3-month course in Egypt, while the same medication costs about $1000 per day in the United States. This strategy makes treatment affordable for developing countries and those who are impoverished. In an attempt to cut down on the black market for these drugs, sofosbuvir is dispensed through Egyptian pharmacies, through a tightly controlled system, where patients receive directly observed therapy, often for free. Interestingly, about 90% of HCV infections in Egypt are genotype 4, which more readily responds to antiviral therapy.
Glucometers as Culprit
SOURCE: Lee EH, et al. Healthcare–associated transmission of Plasmodium falciparum in New York City. Infect Control Hosp Epidemiol 2016;37:113-115.
Person-to-person transmission of malaria is rare but has been reported as the result of contaminated blood products, needle sticks, saline flushes, multi-dose vials, and contact with non-intact skin. Injection drug use in some countries may be the more frequent route for this unusual event. While sexual transmission of malaria does not occur, congenital transmission may. In a review of malaria cases at our county facility in 1991, one case of P. vivax was identified as the result of congenital transmission in a 1-month-old.
Investigation at a New York City hospital points to a break in infection control practices resulting in occult person-to-person transmission of P. falciparum to a 40-year-old woman, hospitalized for acute cholecystitis, requiring cholecystectomy. She was admitted 2 weeks later to a different facility with fever and thrombocytopenia, with evidence of P. falciparum ring forms on blood smear.
The problem was, there was no plausible explanation for her malarial infection. She had no history of travel, she lived in a group home, which she seldom left, she had received no injections, did not live near an airport, and had no international visitors (making “suitcase” malaria unlikely, with spare mosquitoes hitching a ride in airplanes or in luggage).
No cases of malaria had been reported by the first hospital. While all cases of malaria must be confirmed by an outside laboratory, and reported to local health authorities, investigation revealed that the initial hospital had, indeed, cared for a woman with acute malaria, just returned from Nigeria. Her blood smears were never reviewed for confirmation, nor was the case reported to local health authorities, and she was presumptively treated for falciparum malaria with mefloquine. Light microscopy and real-time polymerase chain reaction (PCR) testing of both patients’ blood smears confirmed P. falciparum. In addition, sequencing revealed 11 of 12 common genetic markers. Pyrosequencing demonstrated 10 identical drug resistance mutations in three genes consistent with an African origin for the organism.
Review of procedures could not pinpoint a certain break in infection control practices at the hospital. Both patients were in the emergency department (ED) at the same time, although in different areas of the ED, and treated by different staff. They were hospitalized on the same ward. Blood draws were performed by different phlebotomists, individual saline flushes were used, and parenteral therapies were administered with fresh tubing and bags. The only suspect source was the glucometers. Both patients had blood sugar checks, although documentation was lacking to directly compare staff and devices used between patients. Further investigation revealed that glucometers were not routinely nor adequately cleaned after use.
In the end, a definitive source for transmission was not identified, but in the absence of any other explanation, a breach in Infection Control practice probably related to poorly cleaned glucometers was believed to be responsible. Ironically, a recent investigation of transmission of an MDR organism in our hospital led to the conclusion that glucometers may have been the source. Observations of ATP testing of glucometers at our site revealed that these devices are well cleaned on the top, bottom, back, and front, but both sides (where they are being held) can have high ATP readings, despite apparently adequate cleaning. How can you hold a device and clean it at the same time?
Shorter Isolation Times for TB
SOURCE: Floe A, et al. Shortening isolation of patients with suspected tuberculosis by using polymerase chain reaction analysis: A nationwide cross-sectional study. Clin Infect Dis 2015;61;1365-1373.
Patients with suspected tuberculosis are frequently masked and placed on voluntary home isolation — or hospitalized — until serial sputum AFB smears are negative and the patient has been cleared to return to work. Patients may miss work or school, may be removed from their family as a precautionary measure, or require prolonged hospital stays in isolation until cleared.
In an effort to determine whether a single sputum sample for polymerase chain reaction (PCR) testing for M. tuberculosis can guide the need for isolation, more than 53,000 sputum samples from 20,928 individuals were assessed. A total of 1630 had culture-confirmed MTb. Of these, 1274 had more than three sputums obtained; 856 had a positive AFB sputum smear obtained 14 days before or after a culture-positive specimen; and 486 had PCR testing performed on more than one sample. Of the 722 patients with either a positive smear or PCR test, 74.1% were smear-positive and 81.4% were PCR-positive.
Only 9 people (2.5%) with culture-confirmed MTb who had provided three or more sputum specimens, at least one of which was smear-positive, had a negative PCR. Eight of these smear-positive/PCR-negative cases had only one sputum that was smear-positive, and five had very low-grade smears. In addition, while most of the concordant smear-positive/PCR-positive samples were obtained within 1 day, there was a trend for the discordant samples to be obtained farther apart (median 4 days, range 1-6 days). In those people who provided only two sputum specimens, at least one of which was smear-positive, seven patients (0.9%) were smear-negative.
Sixty-five patients with one or more PCR-positive samples were culture-negative. Of these, various other mycobacterium were isolated, including M. avium (n = 1), M. gordonae (n = 2), M. bovis (n = 1), and nine others that were untypeable (but could feasibly have been poorly growing MTb). Many of these patients had begun antituberculous therapy.
MTb PCR was positive for more than 97.5% of the smear-positive, culture-confirmed cases, who had provided three or more sputums. MTb PCR testing of sputum specimens may provide rapid confirmation of those patients with MTb, allowing a larger number of patients without MTb to be quickly cleared and returned to work and their families. A small percentage of patients (2.5%) may yet prove to have MTb, but these data suggest that most will have low-grade smears, and are not as likely to be contagious. Whether smear-positive/PCR-negative being ruled out in-hospital should be removed from isolation seems less certain; our hospital still requires patients with confirmed MTb to remain in isolation for a full 2 weeks of therapy and three negative sputum smears.
Discordant smear-positive/PCR-negative results in this study may have been the result of poor-quality specimens submitted for PCR testing. This suggests that only those smear-positive specimens be submitted for PCR testing. This is something our laboratory has attempted but finds limiting because of the larger volume required to perform both tests. Perhaps two negative PCRs obtained on good induced sputums in suspect cases would be adequate for removal of respiratory precautions in-hospital. These data also highlight the importance of submitting quality samples to the laboratory for AFB smear and PCR testing. Unless patients can readily produce productive phlegm, I prefer sending patients to the respiratory therapy lab for good induced specimens. Suspect patients, generally with smaller infiltrates, who are unable to produce good specimens are referred to pulmonary for bronchoalveolar lavage.
Diagnostic Puzzle? Solved by The New York Times; Glucometers as Culprit; Shorter Isolation Times for TB
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.