TOPSHOT - A staff member of the Congolese Ministry of Health prepares the sampling equipment to ... [+] perform a COVID-19 test at a private residence in Goma, northeastern Democratic Republic of Congo, on March 31, 2020. One positive case of COVID-19 coronavirus was reported on March 30, 2020 in Goma, capital of North Kivu Province and a city of more than one million inhabitants, bringing the total for the Democratic Republic of Congo to 98 positive COVID-19 cases including 8 deaths. (Photo by Alexis Huguet / AFP) (Photo by ALEXIS HUGUET/AFP via Getty Images)AFP via Getty ImagesThe World Health Organization is responding to an unexplained illness occurring in the Kwango province in southwest Democratic Republic of the Congo. The illness has been ongoing since late October. According to the DRC Ministry of Public Health, 394 cases and 30 deaths have been reported so far in the Panzi health zone. At this time, a cause has not been determined, but symptoms include fever, cough, headache, trouble breathing and anemia, according to the WHO. Although this appears to point to a respiratory illness, more information is needed to make a determination. A team from WHO has launched to support local authorities in determining a cause with kits for sample collection and diagnostics, medications, as well as public health response. As an infectious disease and public health physician watching this situation unfold, there are some key aspects I am interested in knowing, which are determined through basic outbreak response.The Initial Steps Of Outbreak ResponseThere are multiple steps to an outbreak investigation, but the first step is always to keep an open mind and determine whether this really is an outbreak. If so, are we dealing with a single disease or multiple different illnesses that are being lumped together? Are the number of ill patients being counted twice, making it larger than it is? These are some common challenges to work through at the very beginning of an outbreak response.Characterizing The IllnessesIf we are convinced this is an outbreak, we want to characterize the illness. In order to do so, it is best to have boots on the ground, hence the reason WHO has launched a team to augment the local care providers and health authorities. This process begins with interviewing patients and the medical providers who have cared for cases to develop an understanding of the patients symptoms and signs, including physical exam findings, laboratory tests, and imaging results, such as x-rays.Armed with a better picture of the illnesses, health authorities will develop a case definition, which summarizes the key features of the illness. Usually, it is better if these are objective and they often include a time period. For example, a case might be defined as anyone who became ill from early October or November until now with a fever, cough, and headache. That is very broad. We usually want to start broadly so as not to miss anyone, but as we learn more information, it is helpful to eventually narrow it down. Once we have a case definition, we can search for and establish a list of cases.Making A DiagnosisIn order to make a definitive diagnosis, we need laboratory results. The complaints in the initial reports sound consistent with an influenza-like respiratory illness, but multiple pathogens can cause that constellation of symptoms, including non-respiratory pathogens. We might want to start with respiratory specimens, such as nasal and throat swabs in addition to blood and sputum samples to test for viruses and bacteria. If any patients have had imaging, such as chest x-rays, those would be reviewed. If the patients have other types of symptoms, those may guide the investigators to obtain other samples, such as stool or urine. They also might be interested in obtaining autopsy specimens from individuals who may have died from the disease.MORE FOR YOUWith the specimens obtained, there are various methods we use to make a diagnosis, including running basic tests for blood counts, blood chemistries, reviewing samples under the microscope, trying to grow bacteria, running PCR tests for DNA and RNA, and even multiple tests for different pathogens simultaneously (called multiplex tests). Armed with those results, wed want to assess them for commonalities or unique aspects to determine if we are dealing with single or multiple causes of the illnesses.Managing the OutbreakIf we can make a diagnosis quickly, that will help us determine whether we have a specific antibiotic or antiviral or some other type of medicine to treat the illness or a vaccine to prevent it. If we dont have a diagnosis, we can try to assess what types of treatments appear to be beneficial thus far according to local care providers.Sometimes it can take a while to determine the cause of an outbreak, especially if we are dealing with a new pathogen or one that is hard to isolate in the lab. Regardless, using epidemiology, we can still identify the ways people are infected by looking for patterns in illness transmission. Do family members appear at higher risk after one individual in the household became ill? Similarly, have healthcare providers become ill after caring for patients? This could provide clues that something is transmitted person-to-person, like influenza or Covid. Armed with that information, we can take steps to reduce spread even without having a diagnosis.Currently, we have little information and speculating on the cause may lead us in the wrong direction. As UCLA Professor Anne Rimoin, who has done a lot of work in the DRC, was recently quoted as saying, It could be anything. It could be influenza, it could be Ebola, it could be Marburg, it could be meningitis, it could be measles. At this point, we really just dont know.No doubt well be learning more in the next few days. At that time, it will be easier to make a more informed assessment of what to expect next.