​Fall 2016

​APHL is using the lessons learned in-country through PEPFAR programs to support Global Health Security Agenda (GHSA) initiatives involving public health laboratories around the world.

Strengthening Lab Systems Under GHSA

​by Nancy Maddox, MPH

How does an outbreak begin? In the case of the 2013-2016 Ebola epidemic, it started with Emile Ouamouno,  a two-year-old boy who lived, and died, in a Guinean rainforest village, hard by the borders of Liberia and Sierra Leone. Emile’s mother, three-year-old sister and grandmother were next to succumb. By late 2014, over 13,000 cases were reported in West Africa, and international responders poured into the region.

"They came in emergency mode," said Alpha Diallo, PhD, HCLD/PHLD(ABB). But eventually, he said, "as Ebola virus disease cases dwindled, the [mobile international] laboratories closed. And as they closed, they left nothing behind them. ... Somebody said, 'Everybody came in a tank, like a war zone. And after the war, they took their tanks back.'"

Yet even as the Ebola epidemic was ramping up, in early 2014 world leaders in Geneva, Switzerland, and Washington, DC were celebrating the launch of an ambitious effort to stop outbreaks from happening—the Global Health Security Agenda (GHSA). As part of that effort, Diallo—a Guinean-born scientist who previously managed the Washington, DC Public Health Laboratory Division—was recruited to return to Guinea as APHL’s in-country team lead and senior laboratory advisor.

The “biggest and most obvious” lesson from the Ebola epidemic, according to the World Health Organization
(WHO), is that “countries with weak health systems and few basic public health infrastructures in place cannot withstand sudden shocks, whether ... from a changing climate or a runaway virus.”

Echoing that thought, Diallo said, “It is important that we develop a sustainable [laboratory] infrastructure, and the only infrastructure that is sustainable is a national network of reference laboratories.” His job today is to support the  development of exactly that, so Guinea need not depend so heavily on external assistance.

Overall, the GHSA aims to assure that all 53 participating countries (as of August 2016) implement the revised WHO International Health Regulations (IHR) so they are able to prevent, detect and respond to disease outbreaks in near real-time. Among other things, those regulations (adopted by the World Health Assembly in 2005) require governments to assess all reports of “urgent events” within 48 hours and to notify WHO immediately; to rapidly determine the control measures needed to prevent disease spread; to develop a national public health emergency response plan; to assure linkage among hospitals, laboratories, clinics, health officials and other key entities “by the most efficient means of communication available;” and to provide support for laboratory analysis of patient specimens. As of 2012, fewer than 20% of WHO member states reported full compliance.

In 2015, APHL was awarded its first CDC/GHSA cooperative agreement funds for $4.5 million, to help grow national laboratory systems capable of real-time biosurveillance—the focus of one of 11 GHSA “action packages” developed to accelerate progress toward specific goals. Part of that funding was dedicated to work in Vietnam. In September 2016, the association was awarded a new, five year CDC/GHSA cooperative agreement with over $8 million in Year 1 funding.

In addition to Guinea, APHL is carrying out GHSA-related work in eight other countries: Ethiopia, India, Indonesia, Kenya, Sierra Leone, Tanzania, Uganda and Vietnam.

One crucial, cross-national project is the creation of an International Public Health Service Fellowship that can be customized to address regional or national laboratory workforce gaps. APHL has already drafted a preliminary curriculum, and a pilot program will likely be implemented in Africa.

Said Samantha Dittrich, MPH, APHL’s GHSA manager, “In our interconnected world, an infectious disease threat in one place can pose a threat everywhere. APHL is the only organization that has both the depth and breadth of knowledge and experience to provide the training and technical assistance needed to strengthen public health laboratories, which is integral to improving health security across the globe."

The association’s GHSA work will build on past successes providing laboratory expertise under the US President’s Emergency Plan for AIDS Relief (PEPFAR), a multibillion-dollar initiative begun in 2004 to drastically reduce cases of HIV/AIDS across the world. Now, as then, APHL’s focus is on building sustainable laboratory infrastructures, assisting with national laboratory strategic plans, training scientist-managers and instituting quality management systems.

However, while PEPFAR was geared towards HIV/AIDS testing, the GHSA goal is for participating countries to develop capacity for ten core assays: influenza PCR, poliovirus culture, HIV serology, TB microscopy, rapid diagnostic testing for Plasmodium spp., Salmonella enteritidis culture and four additional tests selected by each country to address its national public health priorities.

Guinea—“People are sober”

Diallo returned to Guinea December 29, 2015—the day President Alpha Condé announced the country Ebola-free, after 90 days with no new patients. “But a month later, another case emerged,” said Diallo. “Plus one more case after that.” As of August 31, Guinea is again Ebola-free, but, Diallo said, “People are sober. They are not as festive as when I arrived.”

Although Diallo says government leaders see the need for coordinated disease surveillance, this lower middle income nation of 12.6 million—42% under age 15—faces many challenges. “During the last two years, everyone was geared just to Ebola,” said Diallo. “They forgot there are other diseases,” such as TB, malaria, dengue fever, schistosomiasis and diarrheal diseases.

The country’s Laboratoire National de Santé Publique, part of the Ministry of Health (MOH), needs assistance. Said Diallo, “If you look at a picture of that laboratory, you would weep. ... It went for 50 years without any infusion of money of any kind.”

Yet, important work has already taken place. This past March, APHL organized a four-day workshop addressing biobanking, biosafety and biosecurity—real concerns in a country with “too many Ebola specimens” left behind
by international responders. In the spring, workers from eight regional hospital laboratories, four national hospital laboratories and the Laboratoire National de Santé Publique attended an APHL-organized workshop on quality management systems. In September, Guinea’s first laboratory quality manual was presented to the MOH. And an effort to train African engineers to certify laboratory biosafety cabinets is ongoing.

In addition, the MOH has established a separate Directorate of Laboratory Services and a national agency for health security. Although routine disease surveillance is only just beginning, there is a weekly meeting for national epidemiologists, laboratory leaders and other public health partners to review communicable disease data supplied by Guinea’s regional hospitals (run by the MOH).

The next items on Diallo’s to-do list are reviewing the needs of the Laboratoire National de Santé Publique to increase diagnostic capacity; to “participate in the revival of laboratory services” in one of the national hospital laboratories in Conakry, the Guinean capital; assessing the training curriculum proposed for Guinea’s first continuing education school to “make laboratory technicians into laboratory technologists;” and identifying a resident molecular microbiologist to work at the national Hôpital Ignace Deen and Laboratoire National de Santé Publique, both in Conakry.

Above all, said Diallo, “We have to be able to support epidemiological surveillance.”

Kenya—“We don’t want information islands”

Three thousand miles east of Guinea, below the Horn of Africa, Edwin Ochieng, MBA, is also considering the needs of a modern public health system. “We don’t want information islands,” said Ochieng, APHL’s in-country lead consultant for Kenya. “From the patient’s point of view, it should be one system.”

Work in Kenya—a lower middle income nation of about 46 million—has progressed beyond the basics. The National Public Health Laboratory in Nairobi boasts five reference-level, sub-laboratories that test specimens coming from hospital labs in Kenya’s 47 counties. APHL’s latest project here, still ramping up, will focus on training and technology for identifying microbial markers of antibiotic resistance.

This level of sophistication is important in a region known for emerging pathogens. A 2004 chikungunya outbreak here spread to the Indian Ocean Islands and from there to parts of Europe, before crossing the Atlantic Ocean and precipitating a massive outbreak in the Caribbean in 2013-2014. Since then, local chikungunya transmission has been documented in Texas and Florida.

Altogether, the association has been involved in projects in Kenya for about ten years, initially supporting the development of a national laboratory strategic plan and helping to implement electronic laboratory information management systems (LIMS) in select facilities, beginning with the HIV, TB and microbiology reference labs within the National Public Health Laboratory and progressing to large hospital labs in Mombasa, the Rift Valley and Coast Province. In all, the association has provided technical support for LIMS implementation in 14 major laboratories.

Said APHL consultant Rufus Nyaga, BBIT, “We’ve been able to integrate LIMS with laboratory equipment, so test reports are automated and there is improved turnaround time.”

Moreover, he said, “We’ve also been able to integrate LIMS with external systems. Remember, the LIMS is in the laboratory. But now it is linked to the doctor’s office. By the time he is walking to the laboratory, we already know the patient is coming. When the test is done, the result goes to the doctor’s health information system.”

The turnaround time for virologic tests—from sample receipt to results reporting—was once as high as 90 days. Today it is three.

APHL is now transitioning the LIMS support to Kenya’s MOH. The next step is to create one seamless uber-system for data exchange among laboratories, hospitals and national health officials, and a technical working group is already meeting to figure out the details.

A second APHL initiative is laboratory mapping—documenting the capabilities and testing capacities of all laboratories in Kenya, so, said Ochieng, “if there is an outbreak in any part of the country, the MOH will know the nearest facility that has the capability to test that specimen [for the outbreak pathogen].” A questionnaire focusing on priority diseases—cholera, measles, anthrax, brucellosis and others—has been developed and an electronic survey system selected. Data collection will begin late 2016.

A third critical activity centers on data quality—instituting a system for external proficiency testing to gauge the accuracy of test results and identify training needs. APHL has been managing the effort for the past two years and has achieved a laboratory participation rate of 95%. Ochieng and Nyaga are now in discussion with the MOH regarding the creation of a national repository for all external quality assurance data.

Vietnam—“All they need is a computer and an internet connection.”

Vietnam was one of the first countries APHL worked with under PEPFAR and one of the first to begin work under the GHSA. This populous nation of 93 million has long borders and a busy commercial life, with $159 billion in exports in 2015, including textiles, seafood, rice and electronics.

Ken Landgraf, MS, a CDC advisor from the QED Group consulting firm, has been working in-country here for the past 2.5 years. He said, “One of Vietnam’s biggest trading partners is the United States, but there’s also lots of trade with China, a lot of poultry crossing borders and lots of opportunities for new flu strains to arise in the region. Antibiotic stewardship is very limited.”

Strengthening the country’s disease surveillance, said Landgraf, is a “win for everyone.”

As in Kenya, a hallmark APHL activity has been LIMS implementation. Reshma Kakkar, MA, APHL’s global health LIMS manager, said when she arrived here in 2005, “all of the laboratories we saw used paper-based systems,” including the national public health laboratory. “Nobody knew what a LIMS was.”

She said, “[T]hey were already fairly organized and somewhat standardized. ... What we sensed was they didn’t necessarily want a proprietary LIMS they would have to keep paying for in the long run. We had to figure out an optimal solution that was sophisticated enough to support a variety of tests, but that also could be in a sense owned by them, so they would have control over it.”

The answer was OpenELIS, an open source LIMS designed by three US public health laboratories. Fast forward to 2016, and that system is now in 39 Vietnamese laboratories.

During a March 2016 visit, Kakkar met with the laboratory director in a large, pediatric hospital in Ho Chi Minh City. The hospital’s 400 doctors and 800 nurses see between 5,000 and 8,000 patients each day. The laboratory—now accredited under ISO 15189—performs seven million hematology tests per year. When samples arrive at the laboratory, they are tagged with the same barcode appearing on the accompanying paperwork with patient information. Doctors no long write test requests out longhand. Transcription errors are way down, and test data is searchable: “You don’t have to flip through books. Now they can actually do some analysis of the data.”

APHL is now piloting a system for electronic test ordering and results reporting at the arbovirus laboratory run by the Institut Pasteur in Ho Chi Minh City, which tests specimens for Zika, dengue and other arthropod-borne diseases for 20 of Vietnam’s 58 provinces.

Kakkar said, “We want to provide a good solution for all these [provincial] laboratories to refer these samples up even before the physical specimen arrives [at the Institut Pasteur] and to be able to securely get results back.” That solution is an online portal delivering “security, efficiency [and] standardization,” while negating the need for special software. “All [the provincial laboratories] need is a computer and an internet connection.”

APHL is also helping to install a LIMS at the emergency operations center (EOC).

Said Landgraf, “The EOC is one of our highest GHSA priorities. These are meant to be information hubs so that decisionmakers and epidemiologists . . . will have all the information they need to monitor case reports, lab reports [and] media related to infectious disease outbreaks. APHL’s work with us on LIMS is going to create one of the key data sources in the EOC network, which will be a very valuable tool.”

The GHSA-assisted push to create a global public health laboratory infrastructure coincides with a resurgence of pathogens, both ancient and modern. Since August, for example, Rift Valley fever has afflicted dozens of people in western Niger, killing more than 20. Zika virus—first identified in Uganda—is now a significant threat in parts of the Americas. And the problem of drug-resistant “superbugs” has become so pronounced that it was the subject of a rare, health-related United Nations summit in September.

The start of an outbreak is an intimate affair—one patient, one family, perhaps a child’s tragic death. But preventing or ending an outbreak is a governmental affair, requiring the ability to definitively detect and track pathogens as they move among local, national and international populations. Needless to say, this cannot be done without the kind of global laboratory network that the GHSA promotes and APHL is helping to strengthen. Said Landgraf, “Laboratory testing is one of the quickest and earliest indicators of an outbreak that we can have.”