A large cruise ship (operated by a company that shall remain unnamed) leaves Miami for a two-week cruise around the Caribbean. On the third day out of port, five passengers experience the sudden onset of nausea and abdominal cramps, followed by periods of watery diarrhea. Four of the ill passengers also experience vomiting, and most of them have headaches, myalgias, and/or abdominal pain. By the mext morning, 37 more passengers have become ill with the same symptoms, and all but one of those who became ill the day before are still acutely symptomatic. Most of the victims are adults. The ship's doctor examines all of the sick passengers. Vital signs are generally normal, except that about 1/2 of the patients have a low-grade fever (typically 38 C). The physical examination is unremarkable. The ship's physician has a microscope and examines several stool smears, but she sees no signs of red blood cells, leukocytes, ova, or cysts. The ship does not have a medical lab, so no other tests are done. The next day, 86 more passengers have become sick with the same symptoms and most of those who were infected earlier are still symptomatic. At this point the company decides to cancel the cruise and take the passengers to the nearest port where they can get more extensive medical care. The ship arrives at an appropriate port about eight hours later. By then, a few more passengers have become ill, but some of those who became ill on the first or second day of the outbreak now appear to be recovering on their own. Lab tests done for the passengers who are still sick confirm that their stool samples do not contain red blood cells, leukocytes, ova, or cysts. Routine cultures for bacterial gastrointestinal pathogens are all negative.

Question 9.1: What is the most likely causative agent?

The lack of ova or cysts in the stool samples argues against a parasitic pathogen. The fact that the stool cultures were all negative argues against a bacterial pathogen, but the standard culture for GI pathogens only detects some of the most common genera like Salmonella and Shigella. (Specific tests must be ordered when microbes not covered by the routine stool culture are suspected causative agents.) So, a bacterial infection cannot be ruled out, but given the lack of obvious evidence for one, a viral infection is a very good possibility. The frequent viral causes of diarrhea are rotavirus and Norwalk-like viruses. Norwalk-like virus is a bit more likely in this case because most of the victims were adults. The symptoms are consistent with Norwalk like virus infection as well.

Question 9.2: What are the genetic and structural characteristics of this causative agent?

Norwalk-like viruses (NLVs) are members of the Calciviridae family of viruses (also known as the enteric calciviruses). The Calciviridae includes both the NLVs and the Sapporo-like viruses (SLVs), which also infect the GI tract. All calciviruses have a genome consisting of positive (+) sense single-stranded RNA. They are non-enveloped and have a small, round capsid that seems to consist of a single large protein.

Question 9.3: How is this disease transmitted?

The virus is transmitted by hands contaminated through the fecal oral route, directly from person to person, through contaminated food or water, or by contact with contaminated surfaces (known as fomites). In food-borne epidemics, transmission vehicles have included oysters, green salads, and chocolate icing (typical offerings in cruise ship buffet lines). Outbreaks have occurred with some frequency in nursing homes, on cruise ships, and in institutions such as schools and summer camps. Aerosolized vomitus also has been implicated as a route of transmission (gee, that's pleasant). In the present case, transmission was most likely by person to person. Had it been a point source epidemic (e.g., contaminated food), most of the passengers would have fallen ill at the same time or, at least, during a much shorter time frame.

Question 9.4: How common is this disease?

Norwalk-like viruses cause approximately 23 million cases of acute gastroenteritis each year and are the leading cause of outbreaks of gastroenteritis. Infections are year-round, with a clear peak in the winter. More than 80% of adults in both developed and developing countries have antibodies to Norwalk-like viruses. NLVs are responsible for about 90% of all epidemics of nonbacterial gastroenteritis.

Question 9.5: How can outbreaks like this be prevented?

In addition to emphasizing basic food and water sanitation measures, control efforts must include thorough and prompt disinfection of ships during cruises, and isolation of ill crew members and, if possible, ill passengers for 72 hrs after clinical recovery. Suitable disinfectants include freshly prepared chlorine solutions (at concentration > 1,000 ppm), phenol-based compounds, and accelerated hydrogen peroxide products. Cruise ships also should encourage frequent, rigorous hand washing with soap and water by passenger and crew members. Rapid implementation of control measures at the first sign of suspected acute gastroenteritis outbreak is critical in preventing additional cases. Because of their high infectivity and persistence in the environment, transmission of NLVs is difficult to control through routine sanitary measures. When these measures are unsuccessful at interrupting the spread of the virus during an outbreak, more extensive disinfection and a period of time without passengers aboard a ship may facilitate elimination of the virus. At this time, there is no vaccine.

Question 9.6: How is this causative agent detected for diagnosis?

A number of ELISA and PCR-based assays for NLVs have been developed, but they are still experimental in nature and not widely available. In the absence of these assays, detection requires recognition of small, round virions in stool specimens examined by electron microscopy (a difficult and not overly accurate procedure).