Congo: the fight against HAT

"I believe African sleeping sickness is extremely dangerous; it's a threat to human dignity," says Dr. Crispin Lumbala. The desk of his unpretentious office in Kinshasa is piled high with binders full of studies, reports, statistics and analyses on his archenemy. "If you tell a patient he's suffering from sleeping sickness, he thinks he has no more value for the community. He's stigmatized, and the other members of the community think he's abnormal."
With a picture of President Joseph Kabila behind him, his eyes focused most of the time on his notebook in front of him, a mobile or landline phone permanently at his ear – this is how this quiet and well-structured physician and disease-control expert runs the Program for Control of Human African Trypanosomiasis of the Democratic Republic of the Congo.

Dr. Crispin Lumbala, physician, disease-control expert, and Director of the National Program for Control of Human African Trypanosomiasis, Democratic Republic of the Congo.

It's astonishing how much emphasis Lumbala places on the psychological and social aspect of the disease. Dr. Nathalie Strub, Medical Director of the Drugs for Neglected Diseases Initiative (DNDi) in Geneva, which is researching to find new drugs to fight the disease, is much more sober in her approach: "Human African Trypanosomiasis, or HAT for short, is a deadly disease that is most prevalent in Central Africa and infects mainly very poor people living in very remote areas."

Dr. Nathalie Strub, Medical Director of the non-governmental organization (NGO) Drugs for Neglected Diseases Initiative (DNDi), who is engaged in research to find new drugs against neglected tropical diseases

Prof. Philippe Büscher, Director of the Institute of Tropical Medicine in Antwerp, which is working on new, simpler tests for diagnosing HAT, goes into more detail: "HAT is an infectious disease caused by protozoa, i.e. unicellular organisms that live in tissues. You find them not only in humans, but also in mammals, but of course also in tsetse flies, where they live as parasites. The tsetse fly is a blood-sucking fly whose bite can infect people with trypanosomiasis. Since the tsetse fly only lives in Africa, the disease is restricted to Africa."
According to estimates of the World Health Organization (WHO), HAT threatens 57 million inhabitants of this continent's tropical belt, 36 million in the Congo alone.
As Dr. Lumbala explains, "The danger lies in coming into contact with an infected tsetse fly. The place where you live is potentially dangerous if there are infected tsetse flies there – every time you walk somewhere, to work for example."

Prof. Philippe Büscher from the Institute of Tropical Medicine in Antwerp, Belgium, where research is being conducted to find new treatments for African sleeping sickness

Dire that humans and the fly share the same needs and preferences: water and shade. They both prefer to live near river courses with dense vegetation. Places where people set up their huts, cook, work or play, sheltered by trees from the direct sunlight, where they cultivate their fields near the water, fish from the shore, wash their clothes or search for diamonds in the Congo – these are also places where the tsetse fly lays its larvae in the ground and, in the daytime, lies in wait for food: blood
When the fly smells a victim or discovers it with its compound eyes, it flies a targeted attack, drills its proboscis into its skin with a painful prick, and sucks blood and lymph fluid out of the wound. If it has previously stung a person infected with HAT, its saliva will contain trypanosomes, the pathogen of sleeping sickness, which will now be transferred to its victim.
In 2013 this happened at least 5,627 times in the Congo. That's the number of patients who were diagnosed with HAT. There were fewer than 100 sufferers in each of almost all the 23 other African countries affected by the disease. The number of undetected and untreated cases is estimated at about three times higher. The Congo is the hardest hit country with 80% of all infections.

Residents of Mushie on the shores of the Kasai River, which is simultaneously the habitat of the tsetse fly, so that the local population is always at risk of being infected with sleeping sickness.

Nevertheless, by historical comparison these are encouraging figures. On the threshold of the 20th century, sleeping sickness still claimed around 800,000 lives in equatorial Africa. The colonial powers suppressed the disease through decades of comprehensive studies and treatment, as well as intensive efforts to combat the tsetse fly. By 1960 it was almost eliminated, and only 4,000 cases were reported.
Peter Holmes, Professor at the University of Glasgow and Chairman of STAG, the WHO's Strategic Technical Advisory Group on Neglected Tropical Diseases (NTDs), says: "Sadly, the disease was later neglected, and the number of cases rose again to epidemic proportions in some areas, aggravated by national uprisings, wars and a lack of healthcare services for patients."
By 1995 the WHO estimated that there were 300,000 cases. In a comprehensive campaign, the organization coordinated all international partners to bring about political decisions and to mobilize financial resources from both the private and public sectors. This led to an increase in technical and logistical assistance, better availability of medicines and treatment, and stronger support for the development of new diagnostic methods and active substances.

HAT patients at Bandundu Ville hospital taking Lampit, one component of Nifurtimox-Eflornithin combination therapy, or NECT.

2009 brought a breakthrough with the development of NECT, Nifurtimox-Eflornithine combination therapy, a treatment for the second, more severe stage of the disease that is more effective and easier to administer and has fewer side effects. Until 2012 all these efforts brought cases down again to 7106, which led to a bold plan:
On January 30, 2012, the London Declaration on Neglected Tropical Diseases was signed by representatives of the WHO, the World Bank, the Bill & Melinda Gates Foundation, the 13 largest pharmaceutical companies like Bayer, governmental organizations like USAID, non-governmental organizations like DNDi, and several governments. Its objective was to completely eliminate – or at least bring under control – ten neglected tropical diseases, including HAT, by 2020. In the spotlight of all activities due to the large number of people affected - the Democratic Republic of the Congo.

The pharmacist of Mushie hospital with Lampit, the drug with the active ingredient Nifurtimox donated by Bayer for use in NECT

As the coordinator of the Congolese national program for the control of sleeping sickness, Dr. Lumbala is responsible for overall logistics in all the provinces of the country. Furthermore, he is constantly updating the rules for combating the disease on the basis of the latest research findings, and monitoring compliance with these rules. Finally, he campaigns for money, materials or logistical support. He receives this from partners such as the WHO. For example, this is the organization that distributes the drugs with the active substances Nifurtimox and Eflornithine provided free of charge by Bayer and Sanofi for the NECT treatment. It also distributes the funds provided by the two companies for mobile intervention teams, as well as the reagent used to detect the pathogen in the patients' blood. The drugs are physically delivered by Médecins Sans Frontières (MSF), an organization operating in 70 countries providing emergency assistance to victims of armed conflict, epidemics and natural disasters.
Lumbala also goes out into the field himself, because "sometimes you can't really judge the needs in the field from your office. For example, it sometimes happens that the people there aren't getting paid; that patients with sleeping sickness who are taken to a hospital don't get a bed; or that there is no water or sanitation facilities. But you can't know that from here. You have to go out into the field to find that out."
Getting out into the field means leaving the nine-and-a-half million city of Kinshasa, which is hardly affected by sleeping sickness at all, and going to the sparsely populated hinterland of the almost two and a half million square kilometer country. This is a time-consuming undertaking, simply due to the poor infrastructure. You drive northeast by jeep for up to eight hours to Bandundu Ville, which is about 200 kilometers from Kinshasa as the crow flies. The capital of Bandundu, which is the province most seriously affected by HAT, is laid out according to a checkerboard pattern. It can only be reached by a dirt track. The DR Congo's 3,000-kilometer road network is one of the least dense in the whole world. By comparison, Germany, barely one-seventh of the Congo in terms of surface area, has more than 230,000 kilometers of asphalted roads – about 77 times as much.

Dr. Crispin Lumbala in the field in the small village of Ngantoko, supervising the screening of the population with a mobile intervention team.

13 mobile intervention teams from the anti-sleeping sickness program visit all the villages of the province at regular intervals and systematically examine the entire population. These teams are an immensely important addition to the health centers that are loosely distributed all over the country.
"HAT occurs in two stages," Crispin Lumbala explains. "Especially at the beginning of the first stage there are no specific symptoms. Patients can remain without symptoms for six months, even for one or two years. Sometimes they only suffer from fever and headaches."
As a result, health centers, most of whose staff have not been trained to diagnose and treat HAT, often diagnose it wrongly as malaria or some other tropical disease.
"The sick person is then given an unsuitable drug," Lumbala continues, "which initially may even lead to an improvement, so that physician and patient feel the treatment has been confirmed. But shortly afterwards the sick person's fever breaks out again and he thinks he has not been cured completely"
During this phase, the disease can be transmitted from the HAT patient to other people via the tsetse fly; it can also enter its second phase, in which the trypanosomes attack the central nervous system.
Nathalie Strub, DNDi: "The typical symptoms are then sleepiness during the day, restlessness at night, and, finally, coma and death. In addition, the patients become very confused, sometimes delusional; they have pronounced psychiatric symptoms, which frighten other people, and are therefore highly stigmatized."

Sylvain Baloji Kanga, National Supervisor of the Research Division of the Program for Control of Human African Trypanosomiasis, Democratic Republic of the Congo, with a wall chart used in the fight against the tsetse fly.

"Now there is a risk of permanent damage, even if the correct treatment is given!" emphasizes Crispin Lumbala, who is particularly distressed by this aspect of the disease. "So it's important to actively search for the patients and to find them during the early stage of the disease when they are not yet showing specific symptoms. This is why the mobile teams visit village after village, screening all the people. Not only those who are unwell, but also people who feel nothing at all and don't appear to be sick."
On his way out into the field Dr. Lumbala is accompanied by Sylvain Baloji Kanga, national supervisor of the program's research division. "We analyze how successful the program is and look for ways to improve our strategy," says the 43-year-old scientist about his work. "When we're out in the field we study whether the protocols are being complied with, the techniques are being correctly applied, and the strategies are being implemented in the fight against the disease."

Sylvain Baloji Kanga, Supervisor of the Research Division of the Congolese Program for Control of Sleeping Sickness, explains the dangers of the disease to children in Kutumpay and shows them how to avoid it.

In Bandundu Ville the two meet their colleague Dr. Florent Mbo, who coordinates the program's activities in Bandundu province. "Each of our teams checks a certain number of endemic villages every year," the 46-year-old explains. "Last year it was about 500. However, the proportion of the population that is endangered is very high compared to the number of mobile teams. We can only screen 20% of the people and really need a lot more staff."
If this need could be met, it is his hope that all the benefits of early diagnosis could fully bear fruit – at the medical, individual and societal level: "A patient who is diagnosed early will become healthy again without any sequelae of the disease. By contrast, patients who come into a health center for an examination are often already in an advanced stage of the disease; despite the treatment they will continue to suffer from the sequelae for a long time and thus become a burden on the community."

Dr. Florent Mbo, Coordinator for Bandundu Province of the Program for Control of Human African Trypanosomiasis, Democratic Republic of the Congo, in front of one of the Program's few (aging) jeeps.

Lumbala, Baloji and Mbo are on their way to Mushie, which is best reached from Bandundu Ville by water. About 15,000 kilometers of the Congo and its tributaries are navigable, as are the Kwilu, the Kwango and the Kasai, via which you can travel the 60 kilometers north-west to Mushie in about three hours. In early September, at the end of the dry season, the rivers carry little water. Numerous islands divide the kilometer-wide rivers into several arms. The captain of the narrow, long motor boat often has to circumnavigate sandbanks close to the water surface, or interrupt the journey to remove water plants from the propeller.
Although these are the country's main transport routes, there is surprisingly little traffic here. Hardly any freighters interrupt the flat horizon separating the reflecting river from the dazzlingly bright sky. Only rarely do you see a hopelessly overloaded boat full of waving passengers fighting its way through the brown waters. More common are paddlers standing in their dugouts, moving from shore to shore where a few huts made of palm fronds stand every few kilometers, and fishermen wading up to their waists in water, throwing out their nets – right in the middle of the tsetse fly's hunting grounds.

Mushie resident on her way to the public water pipe to wash dishes, a potentially dangerous walk though the habitat of the tsetse fly, which transmits the pathogen of sleeping sickness

This was how Nsole Bompina, 37, caught the disease. He is currently the only HAT patient in Mushie. The 33,000 inhabitants of the small town enjoy two privileges: a Chinese shop – which sells everything from artificial flowers and suitcases to stereo systems and solar panels (although it's hard to imagine who would buy them here) – and a hospital, built by the Belgians during their colonial rule, which makes an extremely neat impression for the region. In the well-swept courtyards of carefully leveled clay hang the freshly washed clothes of patients and their families, who pass the time sitting in front of the light-green-painted wards. Among them are a fisherman named Nsole, 37, his brother and fellow fishermen Lokua, 52, and their sister Isumu, 56, who earns her living as a farmer. Nsole is greatly marked by the disease; he can't stand or walk alone and finds it difficult to talk. His brother and sister wash and feed him every day, putting a total of three of the family's breadwinners out of action.

Family members of patients at the hospital in Mushie sitting in front of a ward. This is where they pass the time when they are not looking after their relatives, cooking food for them and washing their laundry

"When patients receive their diagnosis, they're usually already at a stage in which they can no longer work or look after themselves or their family," explains Crispin Lumbala, describing the patients' precarious situation. "For this reason, the people usually don't have to pay for their treatment. But if they're in a hospital that doesn't specialize exclusively in patients with African sleeping sickness and is not taking part in the program against the disease, they have to pay for their stay. That's why some patients delay their treatment or miss follow-up examinations, because they can't afford the costs or have to look after their family. In this way it can sometimes happen that we lose patients and they die of the disease."
So Nsole is lucky that his family supports him in such an exemplary way, despite the difficult consequences. His brother even paddled him to Mushie with his dugout canoe in a 14-hour tour de force. "When I came to him, he could neither sleep, nor speak, nor eat," emphasizes Lokua. "His skin was flaking and he was terribly choleric toward his wife. But people where we live know these symptoms. If a person strikes someone for no reason, and also has fever and a headache like with malaria, they know that this man is suffering from sleeping sickness."

Nsole Bompina (m.), fisherman infected with HAT, with his sister Isumu and brother Lokua, who paddled him to the hospital by dugout canoe in a fourteen-hour journey.

Dr. Guylain Mandula, director of the hospital and attending physician, confirms this. "The patients suffer from different behavioral disorders. If there are signs of depression, the people come to us straight away, because in this region they quickly fear that a spell has been put on the patient, that a fetish might be involved, or that he might have violated certain customs and traditions.
Some people who know something about sleeping sickness bring the sick people to us if they notice a change in someone's behavior: if someone talks a lot more than normal, doesn't know what he's doing, is restless, and is constantly leaving the house for no reason or often cries out. If they know they're living in an endemic area, they'll come to the clinic for an examination."
On the one hand, this is encouraging evidence of the effectiveness of the educational efforts being made by the mobile intervention teams. On the other hand, it shouldn't be taken for granted.
Prof. Holmes from the WHO's STAG: "People who live in poverty and have no education are very suspicious toward outsiders getting involved with treatments they don't know. Clinical teams are often accused of bringing the disease into a village in the first place, rather than examining the people and solving a problem they already had beforehand."

Dr. Guylain Mandula, director of the hospital in Mushie, takes the view that the disease cannot be defeated in the long term

"The people often also refuse to take part in the examinations conducted by the mobile intervention teams," adds Crispin Lumbala, "because they're afraid of the diagnosis and that the whole community will hear about their disease."
Professor François Chappuis is the Medical Advisor of the Swiss Section of Médecins Sans Frontières, who screen people in the eastern Congo with their own mobile teams. His conclusion is that "our communication has to work very well. We have to work together with the community leaders and representatives and must accept that sleeping sickness doesn't have the highest priority for them."
Even so, lots of people come to the screening session in Ngantoko when Crispin Lumbala, Sylvain Baloji and Florent Mbo arrive there the next day. The small village, 80 kilometers north-east of Mushie, is only accessible by boat on the Fimi. Here there is even less traffic on the river. The endless savannah to the right and left of the shore seems even more thinly populated.

Mobile intervention team at work in Kutumpay, where the population is actively being tested for sleeping sickness, as in the whole Democratic Republic of the Congo.

No sooner does the boat approach the landing stage than the visitors are greeted by hordes of frolicking children. Women in hitched-up skirts are washing clothes in the shallow waters near the shore. Fishermen offer their wares: freshly caught or dried and salted fish. Snow-white, peeled manioc is glistening in the sunlight on man-high wooden frames. Colorful cloths are drying between palm-frond-roofed huts whose façades are unrendered, but reveal skilled masonry. The mobile intervention team now sit quietly at wooden tables in front of their equipment under large, shady trees on the central square of the village. As we walk through the village, the entourage and the volume level grow continuously. The latter is surpassed only by the megaphone announcements of the village crier, who struts around with measured step.
Dr. Lumbala explains his function: "This member of staff is responsible for explaining the team's aims to the population; he tells them that the team is coming and calls on them to participate in the screening before the mobile team reaches the village."

Announcer from the mobile intervention team in Ngantoko, who already informed the population about the upcoming tests several days before they began.

He continues this work on the day of the screenings right through until the afternoon. The aim is not only to spread the news, but also to help overcome economic, psychological and cultural forms of resistance among the population. Professor Chappuis of MSF: "The people we examine have so many other vital priorities that not going to work for a day is a real investment. They live from day to day. And many of them are also afraid of the tests."
Sylvain Baloji Kanga adds more reasons why some people stay away from the examinations: "In Africa, diseases are often thought to be related to a curse, a malediction or a sin. Falling ill is the punishment. This is why you don't get 100% participation from the population. Those who believe in their traditions stay at home. Only the people who no longer believe come to the nurses to be examined."

The medical director of the mobile intervention team in Ngantoko examining lymph fluid with a microscope, pictured with a patient whose first HAT blood test had been positive.

In Ngantoko, participation is lively. Only every now and then does a person hesitate at the last moment and – after a long, sometimes heated discussion with the team's secretary – finally decides against an examination. All those who are willing to take part give the secretary their name and date of birth; he then gives them a small control slip and sends them to the second stage of the screening process.

Inhabitants of Ngantoko village report to the secretary of the mobile intervention team to have the HAT test; they leave their personal data and subsequently have a blood sample taken

Here, a laboratory technician takes a blood sample with a well-rehearsed prick into the person's fingertip – suspiciously watched by all the bystanders – and draws it into a capillary tube. The tubes are stacked in a holder on the table of the director of the medical team, who conducts the CATT: the Card Agglutination Test for Trypanosomiasis. This serological test determines whether a person has come into contact with trypanosomes and has developed antibodies. A drop from a suspension of purified, fixed and stained trypanosomes and a drop of the fresh blood are mixed on a test card and placed into a rotator. If the tested person's blood contains trypanosomiasis antibodies, the cells can be seen to clump together or agglutinate after a while. The test is then positive; however, this does not confirm that the person has HAT.

A resident of Ngantoko village having his blood sample taken. After registration, this is the second stage of the process of screening the population for HAT by a mobile team

The finding is noted on the control slip, and the patient then returns to the secretary, who neatly copies out all the data by hand into the log. He discharges the patients whose test is negative, who can then go home. However, if the test is positive, he sends the patient to the third stage of the team with a corresponding endorsement on his slip.
Here a nurse first checks with a knowing hand whether the lymph nodes in the patient's neck are enlarged. If this is the case, lymph fluid is extracted and examined for trypanosomes under a microscope by a lab technician. If the lymph nodes are not enlarged, and no pathogens are found in the lymph fluid, the nurse takes another blood sample, this time from the vein, and the technician looks for trypanosomes there. If there are no trypanosomes in the blood, but other signs of an infection, a lumbar puncture is carried out on the spot to be absolutely sure whether there are any trypanosomes in the cerebrospinal fluid.
Only if one of these tests is unequivocally positive – and this must be checked and expressly confirmed by the team's medical director – is the examined person classified as a patient who has HAT and must be treated.
The lumbar puncture – in which a needle up to 15 centimeters long is inserted into the spinal canal through the spaces between the lumbar vertebrae – is often an extremely unpleasant procedure and frequently provokes fierce resistance from patients.

The CATT, the Card Agglutination Test for Trypanosomiasis, is conducted during screening in Ngantoko; the aim here is initially to determine whether a person has had any contact with the pathogens of the illness.

"If the disease has been detected, it's not easy to persuade the person to have a lumbar puncture," explains Alexandre Mbukatoto from experience. He is the medical director of the mobile intervention team which is visited the next day by Lumbala, Baloji and Mbo in Kutumpay, 120 kilometers south of Bandundu Ville. "The sick people find it easy to accept a lumbar puncture if they have suffered a lot beforehand. However, after the treatment they almost systematically reject another puncture which is again necessary six months later."
All the more encouraging is the breakthrough made by the DNDi research team in the search for a new drug against HAT, which is currently being tested on patients. The patients would only have to take one tablet once a day – unlike NECT combination therapy, where Eflornithine is administered once daily, as an infusion, and Nifurtimox several times a day in tablet form.

Inhabitants of Ngantoko village at the third stage of the mobile intervention team's procedure, where the lymph fluid, venous blood and – if necessary – the cerebrospinal fluid are tested for pathogens of African sleeping sickness

In addition to easier administration, the new medicine also has a positive side-effect. Nathalie Strub of DNDi: "Our treatment would be very effective in treating second-stage patients who are seriously ill, but at the same time it would also be well tolerated by first-stage patients. For this reason, a lumbar puncture is not necessary to determine which treatment we must apply."
However, it will still be the case that only a lumbar puncture can clarify whether a patient has definitely recovered. So the mobile intervention teams would still have to reckon with resistance from their patients. This is exactly what happens in Kutumpay – albeit for other, unexpected reasons:

Lola Ngafutu, a farmer, with two of her six children, who, because of the absence of her husband, has refused to have the lumbar puncture that could confirm that she is now healthy again.

Sylvain Baloji is teaching a group of children about the dangers of trypanosomiasis in the shade of a tree using old wall charts. While he is listing the symptoms of the disease out loud, sheet by sheet, and the children dutifully repeat what he says, chanting in unison, the examination procedure one tree further away suddenly comes to a halt. A woman with two children, one on her arm, one holding her hand, is shaking her head vigorously and arguing with the nurses. Later she says her name is Lola Ngafutu; she is 39 years old, had six children and is a farmer's wife. "I had sleeping sickness two years ago. Today I'm here because the mobile intervention team has to do a follow-up examination. But I can't allow that because my husband isn't here. He actually wanted to join me here, and he has to know what happens to me. I can't do this without his permission."
Alexandre Mbukatoto just shrugs his shoulders. He knows he has to accept such unwritten laws, even if they make no sense from a medical point of view and are dangerous for the patient. "You can't force them," he says in resignation. "She has the right to do what she wants with her own body."
However, the chances that Lola really is cured are good in this case, because the baby on her arm was born after her treatment and is healthy. Apart from the sting of the tsetse fly, blood transfusions, and extremely rare transmissions by sexual intercourse, the infection of an unborn child by the sick mother the only way sleeping sickness can be contracted.

Alexandre Mbukatoto, medical director of the mobile intervention team in Kutumpay, is firmly convinced that African sleeping sickness cannot be effectively combated without the mobile intervention teams.