Infectious Disease Surveillance in Times of Calm and in Times of Storm
Infectious Disease Surveillance in Times of Calm and in Times of Storm
Lab Culture discusses different surveillance approaches for optimal disease tracking, proving especially timely in light of the current Ebola outbreak
No individual doctor, nurse, clinical laboratory professional, or healthcare worker, no matter how dedicated, can single-handedly stop an epidemic. Solving the problem of disease at a population level requires coordinated, population-wide understanding of and response to the disease. To build this broader understanding, countries rely on surveillance systems. Surveillance programmes are designed to detect, verify, report and respond to new cases of diseases of concern, on the principle that the more thoroughly we understand a disease, the more effectively it can be combated.
As the key agents that confirm diagnoses and transfer this information from the point of patient care to the Ministry of Health (MOH), laboratories play a central role in many surveillance activities. To find out more about how surveillance works outside the laboratory, Lab Culture spoke to three epidemiologists who are national coordinators of surveillance programmes for established and emerging infectious diseases (EIDs). Dr. Akin Oyemakinde of Nigeria is the Chief Consulting Epidemiologist at Nigeria’s Center for Disease Control and a Programme Director at the MOH. Ms. Semá Baltazar is the Head of Surveillance Department at Mozambique National Institute of Health. Mr. Zephania Irura of Kenya is the Focal Laboratory Person in the Department of Disease Surveillance and Response at the Kenya MOH. Lab Culture also spoke to Dr. Angela Amayo, Associate Professor Department of Human Pathology (Clinical Chemistry Unit), University of Nairobi, who is also an Honorary Consultant in Laboratory Medicine at Kenyatta National Hospital.
It is imperative to know as much as possible about the disease burden and how it changes over time. However, if every laboratory technician and doctor filed a separate report for every case of every disease they diagnosed and treated, resource-limited healthcare systems would collapse under mountains of data, not to mention expense. In order to be productive rather than overwhelming, surveillance systems have to be designed with care: clear about a country’s disease priorities, clear about the case definition for a disease, and efficient in analysing the information gathered and directing resources to respond.
There are many approaches to gathering diagnostic and epidemiological information. Diagnoses of a specific disease may be reported in the aggregate over a set time period, or immediately each time they are confirmed; reporting parties may include clinics, hospital laboratories, community health workers; and reporting may be practiced either country-wide or at selected “sentinel sites,” among other strategies. MOHs use this information to create and revise policies aimed at bringing the disease burden down to an acceptable level.
Often times, in addition to passing information about disease forward to more central levels, laboratories and healthcare facilities also receive feedback reports that can help improve case management. For example, combining antimicrobial susceptibility data from many facilities in a district can help guide clinicians’ decisions about an appropriate course of treatment for cases in that region. Furthermore, knowing what diseases are at work in a given region at a given time can heighten doctors’ awareness of possible diagnoses.
Disease-specific surveillance: Many goals, many approaches
All surveillance networks share the overarching goal of situational awareness, or knowing the health status of a population over time, especially as outbreaks evolve and responses go into effect. What is to be done with surveillance data on specific diseases depends on the goals for disease control. Insights gained from surveillance for an entrenched epidemic such as tuberculosis (TB) may be used to direct funds to reduce the disease burden, whereas surveillance for an EID may be intended to detect and halt an outbreak.
Surveillance is a powerful weapon in the fight to control or eradicate vaccine-preventable diseases. By identifying pockets of susceptible population that remain after an initial mass vaccination campaign, surveillance makes it possible to follow up with repeat vaccinations cost-effectively. This strategy of targeted revaccination is widely credited with the eradication of smallpox in the 1970s. More recently, the global polio eradication campaign continues to depend on case-based surveillance to prevent reintroduction. For example, in eastern Kenya, surveillance for acute flaccid paralysis detected 14 cases of polio in 2013, prompting a revaccination effort that reached one million children. The effort appears to have been successful; at the time of writing, Kenya has reported no polio cases in 2014 to date. 
Surveillance can also support vaccination programmes whose immediate aim is disease control rather than eradication. In Nigeria, which this year concludes a five-year campaign to vaccinate the population aged 1-30 using MenAfriVac, a heat-stable vaccine against Neisseria meningitidis A, case-based surveillance for meningitis is now standard. Dr. Oyemakinde describes a new system wherein “all States ensure laboratory confirmation” of suspected new cases of meningitis, and epidemiological data including attack rate and case fatality rate are collected automatically. Laboratory diagnoses have confirmed very low prevalence of N. meningitides A in Nigeria and other countries involved in the MenAfriVac vaccination programme. 
Often the most widespread epidemics are also most closely monitored. Surveillance can help public health officials identify the most pressing needs associated with diseases for which vaccines are a distant dream. Mozambique’s ministry of health uses two strategies for active, noncontinuous HIV surveillance. Antenatal clinic surveillance of pregnant women in 36 sentinel sites across the country occurs once every two years. ANC surveillance procedures in Mozambique are based on UNAIDS/WHO guidelines. At sentinel sites dried blood (DBS) spots are collected to be testes at central level with Enzyme-Linked Immunosorbent Assay (ELISA). UNAIDS’ final report on global HIV relies only on the dried blood spot results. Although rapid testing at the point of care is common especially in pregnancy, a recent analysis showed poor agreement between rapid testing and ELISAs carried out at the reference laboratory. An additional national the national prevalence survey measured HIV prevalence at community level in over 16,500 individuals aged zero to 64 years and assessed risk behaviours in youth, adolescents, and adults. This survey, was conducted with the support of many partners, first tested over sixteen thousand Mozambicans in 2009 and is underway again this year. This year, the survey also includes malaria and immunisation indicators.
Like malaria, TB has significant geographical overlap and a high co-infection rate with HIV. The Stop TB strategy, a programme whose goal is to “achieve universal access to high-quality health care for all people with TB” and reduce the infection’s spread, lists as a high priority people infected with both HIV and TB.  In many countries, new TB diagnoses are passively reported to the MOH by diagnosing facilities on a monthly or quarterly basis. For new tuberculosis cases, the World Health Organization (WHO) recommends that information including the results of sputum smear microscopy, information about HIV co-infection and antiretroviral therapy (ART) status, and case management records be collected and forwarded to the national TB programme. However, not every new case is reported; the WHO estimates that, while about six million cases were reported worldwide in 2012, three million new cases developed but went unreported owing to imperfect diagnostics, limited access to primary healthcare, and lack of consistent legal requirements to report new cases.  It is important for a surveillance system to get a good estimate of its case detection rate, or CDR, the gap between the number of cases reported to the MOH and the true number of new cases. High CDR indicates both an accurate diagnostic strategy and an effective country reporting system. This number can not only tell the weaknesses of available data, but also illuminate gaps in the disease-control system.
The scope of a pathogen’s threat to public health affects the requirements for surveillance sensitivity. When resources are limited and a disease is widespread, a lower CDR may be acceptable; policy decisions can still be made based on statistically representative data. For example, in screening systems for diseases such as neonatal tetanus, where a large number of cases occurring in one place is a cause for concern, even with a relatively low case-detection rate the goal of identifying geographical regions of concern can still be met. On the other hand, in the context of an outbreak with the potential to spread, catching cases at the early stages of an outbreak, before it explodes into an epidemic, can save lives.
Surveillance and response to halt an outbreak: Emerging infectious diseases
For an established epidemic, “we already have the tools in place so that data is routinely collected and analysed. But with this system, we can also pick up new, concerning infections,” says Mr. Irura. If the concern is sufficiently great, such a finding may trigger an active surveillance response. According to Dr. Oyemakinde, the difference between surveillance for an established epidemic and an active outbreak of EID is that “while we wait for cases [caused by an established infectious disease] to be reported…for an emerging disease like Ebola, surveillance is active, [including a] search for contacts, suspects and cases.” When every missed case represents a new possible chain of transmission that may do devastating harm, many more resources are poured into the effort to contain the outbreak. Active surveillance of this scope can be very expensive, so there must be a significant threat to justify the set-up of a surveillance programme.
The first step in setting up surveillance for an EID, says Dr. Oyemakinde, “is to agree on the case definition (suspected, probable, confirmed), and then send out an alert which includes the case definitions…with clear outlines for notification” to healthcare facilities and laboratories around the country. Sometimes case definitions change depending on context. For example during an Ebola outbreak the WHO recommends that the definition of a suspected case be expanded from contacts of confirmed cases to also include anyone with sudden onset of high fever and at least two of a list of other symptoms. A probable case is a person with a suspected case who has been examined by a physician; confirmation, again, depends on laboratory testing.
Nigeria’s Emergency Operations Center for Ebola is a heartening example of how having a pre-existing surveillance infrastructure can give a country the capacity to deal with new challenges. The centre currently coordinating Nigeria’s Ebola operations was founded in 2012 as a command centre for polio eradication, and converted at the start of the current outbreak.  Dr. Oyemakinde, who coordinates Nigeria’s surveillance programmes, has been involved in setting up Ebola surveillance in the country. New measures include thermal screening of incoming and out-going passengers at ports of entry, as well as enhanced surveillance at health facilities and thermal screening of suspected contacts of Ebola patients. This robust surveillance system is one of many factors that have contributed to Nigeria’s control of the Ebola epidemic.
Many of the previously described surveillance programmes monitor infectious diseases that are well known as public health threats, and that are familiar to the community and the doctors treating them. However, it can be difficult to differentiate an EID from its more common, less-virulent symptomatic look-alikes with similar symptomatic profiles. “People are trained to see a syndrome, but don’t have the capacity to distinguish” between aetiologies in a clinical setting, says Ms. Baltazar. She cites as an example a dengue outbreak detected this April as Mozambique’s MOH developed its new sentinel surveillance system for arboviruses. This was the first outbreak of dengue recorded in Mozambique since 1985.  Although the prevalence of dengue has been on the rise worldwide, Ms. Baltazar points out that the long gap may not have been due to an absence of the virus, but rather an absence of laboratory testing, without which dengue is frequently misdiagnosed as malaria.
In such situations syndromic surveillance combined with a strong referral system may be an appropriate response. Syndromic surveillance takes advantage of the fact that many EIDs present as encephalitic or influenza-like illnesses of unexplained aetiology, or that fail to respond to normal treatments.  Dr. Amayo says that although for now “the laboratory system is the weakest link in achieving the ideal surveillance system, especially for infectious conditions,” with limited capacity to identify many pathogens in many local laboratories, referring samples from such cases to a higher-tier laboratory with greater testing capacity is an effective workaround. Kenya’s own dengue surveillance system, established after a 2013 outbreak, operates on this framework. 
The African Cholera Surveillance Network, or Africhol, which Ms. Baltazar coordinates in Mozambique, is another programme undertaking active, syndrome-based surveillance to prevent epidemics before they begin. In zones of enhanced surveillance, where there is some history of cholera, samples and information are collected for every case of acute diarrhoea meeting the case definition.
Consolidating surveillance efforts: Integrated Disease Surveillance and Response
Although the goals for disease control are numerous and vary by disease, many surveillance systems share the same general structure, with laboratories or healthcare facilities reporting to a more central level. Notwithstanding this similarity, the first surveillance systems established tended to focus on individual diseases. Parallel surveillance programmes, with numerous disease-specific diagnosis and reporting structures, tend to multiply the administration required and limit the resources for verification of and response to reported outbreaks.  Furthermore, they can result in warehousing of knowledge about different infections in different offices, where important connections may be missed. Therefore, in 1998 the WHO Regional Office for Africa (WHO-AFRO) introduced the concept of Integrated Disease Surveillance, which sought to bring together disparate surveillance activity within each country. Because surveillance is only the first half of responding to and managing outbreaks and longer-lasting epidemics, the framework is now called Integrated Disease Surveillance and Response (IDSR).
Mr. Irura describes Kenya’s national IDSR programme as “a plan for dedication of resources we have in the country to complementary surveillance activities,” instead of splitting these resources between many separate, redundant activities. Likewise, WHO-AFRO’s technical guidelines for IDSR are clear that IDSR’s purpose is to streamline the existing programmes, rather than to build a whole new system. The goal is to make the system more flexible, more sensitive, and closer to real-time awareness of public health concerns as they arise.
Part of dedicating resources for integrated disease response is setting clear priorities for surveillance. There are a few conditions that under the International Health Regulations must be reported to the WHO when detected; these are smallpox, poliomyelitis, human influenza caused by a new subtype, and SARS. Otherwise, countries prioritise disease surveillance at their discretion; the WHO suggests focusing on diseases that are epidemic-prone; targeted for eradication and elimination; or otherwise important for public health.
“Integrated disease surveillance is a good strategy, but it sometimes has some challenges,” says Ms. Baltazar. Concentrating resources at the same site, she says, can dramatically improve the capacity of healthcare providers at that site. On the other hand, expanding the services provided at the same site means that “in countries with limited human resources, you concentrate a lot of work on the same person,” who must report numerous cases in addition to their normal duties.
IDSR also demands substantial coordination at the district and national levels, both in the development and distribution of case definitions and in the construction of systems for reporting cases. Healthcare workers need to be trained about what is a reportable case and provided with a steady supply of materials for collecting and reporting cases as they arise, and new facilities need to be enrolled in surveillance programmes. In many countries, private laboratories are separate from the national surveillance system and may not be legally required to report cases, which can lead to important miscommunications. During the Kenyan dengue outbreak first reported in March 2013, an investigation team looking for the index case found that two private laboratories in the region had diagnosed dengue as early as two months prior to the first case confirmed at the Kenyan Medical Research Institute.  The IDSR technical guidelines published by WHO-AFRO in 2010 include suggestions for district-level coordinators of surveillance programmes to address some of these challenges.
IDSR tends to focus on diseases with epidemic potential, but it is increasingly apparent that non-communicable diseases are also a threat to public health. “We’re dealing with a double burden,” says Dr. Amayo, warning that overlooking trends in non-communicable diseases could lead to disaster in the future. Dr. Amayo will present a report on laboratory-based surveillance in Kenya at ASLM2014.
On balance, however, the experts agree that integration of disease surveillance and response systems is a move in the right direction. IDSR has made surveillance more visible to governments and other funders as an important component of disease control. Involving the public as knowledgeable health informants has expanded awareness of specific epidemics and of surveillance in general. One of the greatest positive effects is in building capacity. “Building surveillance has required a lot of investment in human resource and laboratory capacity building,” says Ms. Baltazar. The returns on this investment have been substantial; Mozambique’s reference laboratory has dramatically expanded its technical abilities, all while improving data collection about the distribution and prevalence of diseases that previously went untracked. Likewise, during implementation of IDSR in Nigeria Dr. Oyemakinde has seen great advances in case detection and reporting at the healthcare facility level. Mr. Irura and Dr. Amayo agree about laboratory capacity building, noting also that they see more capacity for mobilizing responses to concerning findings.
Most of all IDSR facilitates what Mr. Irura calls a “team spirit” among epidemiologists, veterinarians, clinicians and others invested in public health. By building a system in which all of these parties communicate about health concerns on a regular basis, integrated surveillance and response systems facilitate relationships where they can work together when the need arises. That way no individual doctor, nurse, clinical lab professional, or healthcare worker—no matter how dedicated—has to work alone, especially in times of active infectious disease outbreaks.
By: Laurel Oldach (Editorial Team); Contributors: Akin Oyemakinde, PhD (Center for Disease Control, Nigeria), Semá Baltazar, MPH (Departamento de Vigilância em Saúde, Instituto Nacional de Saúde, Mozambique), Zephania Irura (Ministry of Health, Kenya), and Angela Amayo (University of Nairobi, Kenya); Editor: Michele Merkel, MS (Editorial Team) and Rachel Crane (Editorial Team)
Disclaimer: The views and perspectives expressed by this article’s contributors consist of personal opinions and do not necessarily reflect the official policy or position of any agency.
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Originally published in the November 2014 issue of Lab Culture newsletter.
 “Nigeria’s actions seem to contain Ebola outbreak.” New York Times. 30th September 2014. Retrieved from: http://www.nytimes.com/2014/10/01/health/ebola-outbreak-in-nigeria-appears-to-be-over.html?_r=0