Ebola surge

The need of the hour is for the international community to see how the health care infrastructure in the countries affected by the Ebola virus can be rebuilt and public trust in it restored.

People form a line as soldiers scan them for signs of the Ebola virus disease, as they control people from entering the West Point area in the Liberian capital city of Monrovia, on August 23. The outbreak continues to spread elsewhere in West Africa.

“Here in Liberia, the virus is spreading like wildfire, devouring the life of everyone along its path. Limited health resources, ignorance, stigmatiation, denial, and cultural burial rites are fueling the spread of the disease. Ebola cases are reported in ten of the fifteen counties in our country. I do not have the space and time to elaborate on how ignorance, denial, stigmatiation as well as cultural practices are spreading the virus. But regarding limited health resources, here is the tip of the iceberg. As part of control measures, everyone was advised to call the Ebola response unit for safe transfer of suspected cases and disposal of corpses from communities in and around Monrovia. There are two ambulances to transfer suspect cases to isolation centr and two burial teams for Monrovia. These teams are overwhelmed and it takes about two to three days to respond to calls from communities. The relatives of suspected cases end up transporting the patient in a commercial vehicle, thereby contaminating themselves. The remains of suspected cases who died at homes spend days before the burial team can arrive. Moreover, there is only one treatment centre in Monrovia. The isolation centre is full to capacity and suspected cases are reportedly turned away. When will the spread and death of Ebola stop in the wake of limited resources? I do not know. But I know for sure that contact tracing is not possible and we are overstretched and exhausted.

Besides Ebola directly killing here, others are dying of treatable conditions due to closure of health facilities. Most health facilities in and around Monrovia have been closed for the past three weeks. This followed the failure of most health workers to show up on duty after the death of their colleagues. They fled due lack of equipment as simple as gloves to protect themselves.”

The excerpt from the “Speaking of Medicine” blog site pretty much sums up the prevalent general situation in the West African countries that have been worst hit by the current outbreak of the Ebola virus disease (EVD)—Guinea, Sierra Leone and Liberia—the scale of which is unprecedented in the history of the disease.*

Known earlier as the Ebola haemorrhagic fever, it was identified 38 years ago in two simultaneous outbreaks—in Yambuku village near the Ebola river in Zaire (now Democratic Republic of Congo, or DRC), and hence its name, and in Nzara in Sudan. Virological analyses of blood samples in the current outbreak have identified the causative agent to belong to the Zaire species of the ebolavirus.

Escalating crisis Though the first case of the disease in the current outbreak has now been traced back to a child patient in December 2013 at the Gueckedou prefecture in the Guinea forest region, it was in February that the disease seems to have got a firm foothold in that country. It was only in early March that the public health services of the region realised that they had a severe epidemic of an unknown disease on their hands that could stretch the efforts to contain the spread beyond their capacities, given the country’s extremely weak health care system.

On March 10, both the Ministry of Health of Guinea and Medicins sans Frontieres (MSF), the global non-governmental organisation (NGO) that has been working on malaria in Guinea since 2010, were alerted about clusters of a new disease characterised by fever, vomiting, severe diarrhoea and an apparent high fatality rate. The Ministry in turn notified the World Health Organisation (WHO) of this mysterious disease that Guinea had not seen before.

It was only by mid-March that both the Ministry and the MSF could deploy their workforce to deal with the crisis, but very soon they were overwhelmed by the rapidly escalating crisis. On June 24, the MSF said that the outbreak was going “out of control” and called for a massive deployment of resources in the region. The WHO, however, seems to have been slow in mounting an adequate response to the outbreak, crippled perhaps by the 50 per cent drop in its 2014-15 budget ($228 million) to deal with crises and outbreaks.

“Although WHO is leading the international response to the crisis, it was slow to act at the high level that was needed,” said an August 23 editorial in the journal The Lancet . According to the editorial, it was only on July 31 that the WHO launched its joint response plan calling for $71 million from donors and the deployment of several more personnel to West Africa.

The rapid increase in cases since June, the first case in Nigeria in July and the airlifting of two EVD-affected American health workers in early August seem to have now elicited much greater international response. The World Bank has also come forward with an emergency fund of $200 million to the affected countries. Following a meeting on August 6-7, the WHO’s Emergency Committee termed the current outbreak an “extraordinary event” and said that, given the virulence of the virus, the possible consequences of further international spread were particularly serious. Recognising the need for a much greater and coordinated international response to stop and reverse the international spread, the WHO declared on August 8 that the Ebola outbreak in West Africa was a Public Health Emergency of International Concern (PHEIC). This, of course, does not imply that the outbreak has the potential to turn into a pandemic. Any country with better health infrastructure than these African nations which are constantly strife-ridden and/or have devastated economies should be able to contain the spread quickly if any case is detected.

The disease is a severe acute illness with a high fatality rate of even 90 per cent caused by the Ebolavirus (Figure 1), which belongs to the Filoviridae family of viruses. It is characterised by the sudden onset of fever, intense weakness, muscular pain, headache, sore throat, vomiting, diarrhoea, rashes, impaired liver and kidney function and, in some cases, both internal and external bleeding. The EVD has in the past chiefly occurred near tropical forests of Central and West Africa. It is a zoonotic disease known to be transmitted from wild animals to humans through close contact with the blood, secretions, organs or other bodily fluids of infected animals. It spreads in the human population through human-to-human transmission. The incubation period, from the time of contracting the virus to the onset of symptoms, is two to 21 days.

The African epidemics have been documented to have arisen through the handling of infected chimpanzees, gorillas, fruit bats, monkeys, forest antelopes and porcupines found ill or dead in the forests. The virus then spreads in the community with the infection being transmitted through direct contact (through broken skin or mucous membranes) with the blood, secretions and other bodily fluids of infected people, or through indirect contact with environments contaminated with such virus-carrying fluids.

Unless appropriate control precautions are strictly adhered to, health care workers particularly run the risk of being infected while treating patients with suspected or confirmed EVD, which has frequently happened in Ebola epidemics. Ritualistic funeral ceremonies in Africa involve direct contact with the body of the deceased person, which too can result in virus transmission. The semen of men who have recovered from the disease continues to harbour the virus for as long as seven weeks—in one documented case, for 61 days. Laboratory signatures for EVD include low white blood cell and platelet counts and elevated liver enzymes.

According to WHO data, up to August 20 the total number of clinical cases, including laboratory-confirmed, probable and suspected, and the number of deaths reported since the spread of the disease was detected in February are 2,615 and 1,427 respectively (see Table). The rapidity of the spread and its associated devastating impact can be judged from the fact that between August 19 and 20 alone a total of 142 new cases and 77 deaths were reported from the four affected countries. These figures should be compared with the biggest epidemic until now, which was in Uganda in 2000 when 425 cases and 224 deaths were recorded. Also, according to the WHO, the current data could be a vast underestimation.

Epidemiological investigations have now traced the first case of the outbreak to a two-year-old child who died in Meliandou in Gueckedou prefecture on December 6, 2013. This is now believed to be the epicentre of the current outbreak, the place where the virus was first introduced in Guinea. The spread of EVD to other prefectures of Guinea —Macenta, Nzerekore and Kissidougou, and eventually to Guinea’s capital, Conakry—appears to have been triggered by a health care worker from Gueckedou, suspected to be carrying the disease, who went to a Macenta hospital and died on February 10. This is believed to have set off the transmission chain within Guinea along the road connecting Gueckedou and Conakry.

The crumbling public health infrastructure in Guinea, which is one of the poorest nations in the world, could not obviously track down all the contacts in the expanding infection chain and contain its spread. The highly porous nature of the border that Guinea shares with Sierra Leone and Liberia would have facilitated the rapid spread of the virus to these neighbouring countries as well. The spread to Nigeria, which does not share borders with the affected countries, points to the distinct possibility of wider international spread through air travel.

The first reported Nigerian case was that of a Liberian-American who flew into Lagos from Liberia and became severely ill. He died five days later on July 25. In response, the Nigerian government traced all his contacts for signs of infection. The contact tracing found that both the nurse and the doctor who treated him had also died of EVD on August 6 and 19 respectively. From here the infection seems to have spread to a few others, but, as the Table shows, it seems to have been better contained compared with the situation in the other three countries, given the far better Nigerian health infrastructure. The number of cases is lower and the deaths fewer.

There are five distinct species of the Ebola virus: Bundibugyo ebolavirus (BDBV), Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV), Reston ebolavirus (RESTV) and Tai forest ebolavirus (TAFV). Only the first three are known to have been associated with large EVD outbreaks in Africa. These have caused outbreaks in DRC, Sudan, Gabon, the Republic of Congo (RC) and Uganda. The RESTV, found in the Philippines and China, can cause disease in non-human primates but is known only to infect humans without causing illness or death. The TAFV was documented in a single human infection transmitted from an infected chimpanzee from the Tai Forest in Ivory Coast.

The disease has a high fatality rate and, depending on the African virus species, it ranges from 25 to 90 per cent. The species responsible for the current outbreak, Zaire ebolavirus, is known historically to have a high mortality rate of 90 per cent. But in the current outbreak the rate is less than 60 per cent if only the laboratory-confirmed cases of EVD and deaths are considered. These figures are 1,528 and 844 respectively (Table). Also, the current outbreak has not seen any significant incidence of internal or external bleeding (haemorrhage) in the patients.

Most importantly, there is no specific treatment available for EVD yet. New therapies are being developed and are under evaluation. But these are yet to be approved for clinical use in humans. Since the Ebola virus is regarded as a potential bio-warfare agent, an R&D programme funded by the United States government has resulted in the development of a drug called ZMapp, which is a “cocktail” of three humanised mouse antibodies against the virus. The drug has been found to be effective in a monkey model. Similarly, the experimental drug TKM-ebola against the Marburg virus, which belongs to the same Filoviridae family, is seen to be effective in rhesus monkeys. Although several vaccines have been tested in animal models, none has undergone clinical trials in humans. As of now the only recommended therapy for severely ill patients is intensive supportive care.

To save the lives of the two American health workers who contracted EVD and were evacuated from Liberia, the U.S. government took the extraordinary step of administering the yet-to-be-approved ZMapp to them. The drug seems to have helped the two to recover. However, as Anthony Fauci has pointed out in an article in The New England Journal of Medicine (NEJM), it is not clear whether the drug caused the clinical improvement of the two patients. “With only two cases, conclusions regarding its efficacy should be withheld,” he said.

But following this apparent effectiveness of ZMapp, there was a growing demand for such experimental drugs to be used in the affected countries given the extraordinary situation. Just about a month ago, the WHO had said that it would be unethical to use such unregistered interventions for treating EVD. However, the WHO constituted a special ethics panel, which concluded unanimously on August 14 that if certain prescribed criteria were satisfied, it was ethical to use yet-to-be approved drugs and vaccines.

Based on available evidence, fruit bats (family Pteropodidae), particularly the species Hypsignathus monstrous (hammer-headed bat), Epomos franqueti (Franquet’s epauletted fruit bat) and Myonycteris torquata (little collared fruit bat), are considered natural hosts for the Ebola virus. The geographical distribution of Ebola viruses may overlap with the range of these fruit bats. (map showing geographic distribution of the outbreak). Though, in principle, India falls within the range of these flying mammals, the virus has never been detected on the Indian subcontinent. Although non-human primates have been the zoonotic source of Ebolavirus infection for humans, they are not reservoirs of the virus, unlike the fruit bats. They are accidental hosts, like humans, and EBOV and TAFV outbreaks have been observed in chimpanzees and gorillas.

A study published in April in NEJM by Sylvain Baize and co-workers had determined that the Guinean virus that is in circulation in the current epidemic has 97 per cent identity (homology) with the Zaire ebolavirus isolated in the earlier human outbreaks in Gabon, DRC and RC. From a full-length genome sequencing and phylogenetic analysis, the researchers, however, concluded that the Guinean EBOV formed a separate divergent lineage from the EBOV strains identified earlier. That is, it is not the result of the spread of the EBOV lineage from Central Africa. A more recent phylogenic analysis by Gytis Dudas and Andrew Rambaut from the University of Edinburgh, which was published in May in the journal PLOS Current Outbreaks , has, however, concluded otherwise. According to this study, the Guinea Zaire Ebolavirus is not a new one but belongs to the same lineage as the earlier isolates from DRC and Gabon. The resolution of these conflicting findings may have to wait for further genetic sequencing studies.

Why Guinea? The puzzling question then is how, and in what circumstances, has Ebolavirus suddenly surfaced in Guinea, which has never seen Ebolavirus before. In a paper published in July in PLOS Neglected Topical Diseases , Daniel Bausch and Lara Schwarz speculate on two possibilities of how the Zaire ebolavirus could have travelled all the way to West Africa. One, the virus was always present in West Africa but was not noticed in the absence of any human outbreaks, and two, it was introduced recently into the region. They, however, note that if the virus had been circulating for some time in the region, one would expect a much greater variation in its genetic sequence than the 97 per cent homology with the virus found earlier.

They further go on to argue that if the virus was introduced recently into Guinea from far-off Central Africa, the most likely traveller was the fruit bat, the known wild reservoir of the virus, which can migrate to large distances. Although the virus is yet to be isolated from a bat in the region, exposures through hunting and consuming fruit bats, a practice similar to Central African customs that is known to be common in Guinea too, may have resulted in its introduction into humans.

“Despite the widely promulgated image of Ebolavirus mysteriously and randomly emerging from the forest, the sites of attack are far from random,” Bausch and Schwarz point out in their paper. “[L]arge haemorrhagic fever virus outbreaks almost invariably occur in areas in which the economy and public health system have been decimated from years of civil conflict or failed development. Biological or ecological factors may drive emergence of the virus from the forest, but clearly the socio-political landscape dictates where it goes from there—an isolated case or two or a large and sustained outbreak,” they added. Despite a wealth of mineral and other natural resources, civil governance in Guinea, which has witnessed a series of coups and much strife, has virtually collapsed. The country still possess the eighth lowest per capita income in the world, and the incidence of poverty has been steadily increasing since 2003, the researchers, who have lived in the region during 1998-2008, note.

“The single most important lesson we learned,” wrote Francis Omasawa, who was the Director General of Health Sevices during the Ugandan outbreak in 2000, “was that building and holding public trust by the government and health personnel is the foundation of all control efforts. Ebola evokes fear and apprehension at individual and community levels, which easily results in herd responses, negative or positive. We achieved public trust in Uganda through very intensive communication with the public. The second key intervention we made was the recruitment of the support of community or village leaders.... In Uganda this was achieved by building community trust of the public health system.”

The need of the hour for the international community is to see how the health care infrastructure in these countries can be rebuilt and public trust in it restored.

*As the article was going for print, the WHO issued an update on August 27 with the news of EVD having also spread to the Democratic Republic of Congo (DRC). The Ministry of Health of the DRC notified the WHO that until August 18 it had identified a total of 24 suspected cases of haemorrhagic fever, including 13 deaths.