Mary Nyaburu recalls how, several years ago, one of her nine children convulsed in her arms while she waited at the district hospital in Tororo, a rural area in eastern Uganda. The other women waiting at the hospital urged her to go at once and see a traditional healer who could exorcise the evil spirits in possession of her one-year-old baby. Worried, Nyaburu fled the clinic and found a healer who sold her a concoction as useless in the fight against malaria as the anti-inflammatory paracetamol she had tried earlier that week. The following day, her child could no longer swallow water. Death followed soon after.

A child's grave lies near a hut in Tororo — an all too familiar sight in Uganda. Credit: AMY MAXMEN

Many mothers in Tororo have similarly heart wrenching stories. In small villages across Uganda, a child-size grave lies within a few metres of many of the huts. Young children are particularly vulnerable to malaria. And in Uganda, where 1 in 7 children die before their fifth birthday, this mosquito-delivered disease is the biggest killer. Although some villagers interpret seizures — one symptom of severe malaria — as a supernatural phenomenon, most mothers nevertheless recognize the progression of joint pain, fevers, vomiting and dehydration that comes with the onset of the disease.

That malaria has an inexpensive cure makes these deaths even more devastating, says Grant Dorsey, an infectious disease researcher at the University of California, San Francisco, who works in Tororo for a couple of months each year. “In our clinical trials we've monitored well over 5,000 patients with malaria and they all respond to the therapy within a day or two. So my own feeling is that — at least in Africa where malaria is caused by Plasmodium falciparum — no one dies if treated quickly. The obstacle really just becomes about access to care.”

Rates of malaria incidence and mortality are falling around the world, thanks in part to the widespread distribution of artemisinin-based combination therapies (ACTs), along with insecticide-treated bed nets. Although such measures have come to Uganda, this country of 33 million people is yet to witness much success in reducing the ravages of malaria. In fact, a study published in 2011 claims that the incidence of malaria in Uganda has, if anything, risen since 2005 (ref. 1). In neighbouring Rwanda, by comparison, malaria incidence dropped by 60% between 2005 and 2010 (ref. 2). Uganda's tragic failure to abate malaria has numerous political, geographic, economic and social factors — and illustrates the reality that it takes more than scientific breakthroughs and cheap drugs to solve this persistent menace.

Blood-thirsty swarms

Uganda is a victim of its own lush lands. The moist soil, wetlands and great lakes for which the country is celebrated also provide a year-round refuge for the mosquitoes that transmit the malaria parasite. The World Health Organization (WHO) estimates that, in 2010, the country had more than 11 million cases of malaria — the most in Africa — and ranked it fifth in the number of deaths from the disease across the continent. What's more, Uganda has the world's highest recorded rate of malaria transmission: reaching 1,586 infective bites per person in 2001 in the swampy Apac district near the Nile River. On average, Tororo's rate is less than half this level, but still higher than rates recorded within Rwanda (81 bites per person per year), Kenya (120) and Sierra Leone (541). Children in Tororo can expect to catch malaria several times each year. Compounding this problem is a feeble healthcare infrastructure that cannot manage malaria's toll on the poor. And Uganda is very poor: 81% of its population live in rural areas, where 96% of households lack electricity and 91% do not have access to flushing toilets.

If Tororo wasn't so plagued by Plamodium-infected mosquitoes, bed nets might do more for villagers, says Abel Kakuru, a doctor who collaborates with Dorsey in Tororo. When their study site was in the capital city of Kampala, Kakuru says he saw about one case of malaria every two weeks. “And then we moved to Tororo and although the cohort was half the size, we began to see at least five cases in our study cohort every day,” he says. “The burden here is so heavy that we need multiple interventions, like indoor residual spraying.” But this control measure is too costly to roll out across the entire country — especially in poor places like Tororo.

A steady stream of women clutching infants and small children flows through the gates of Tororo district hospital. Some ride in on the back of bicycles or motorcycle taxis called boda-bodas. Those who can't afford the US$3 ride arrive on foot. Patients will often wait for most of the day to see a doctor, meaning that mothers who accompany sick children also miss a day's work. Waiting in the hospital is Florence Aketch, a mother with a shy 4-year old boy on her lap. Every few weeks, Aketch travels the 7km to the hospital with either her son, who gets ill with malaria monthly, or his twin sister, who becomes feverish slightly less often. Both twins sleep under a mosquito net, but it doesn't seem to matter. She reckons that her children get bitten while they eat dinner just after dusk. Even if they dine inside the house, mosquito-proof sealing or window screens would be of little use: in Aketch's village, straw thatch covers clay or cement huts about the size of a one-car garage. If there's a door, it is a flimsy piece of wood. In short supply Public hospitals in Uganda offer ACTs free of charge. The private sector dropped the price of drugs to about US$1.30 for a 3-day course, thanks to the Affordable Medicines Facility for malaria (AMFm), a programme run by one of the largest malaria-control funders, The Global Fund to Fight AIDS, Tuberculosis and Malaria. The AMFm subsidies have helped slash the cost of malaria treatment in Uganda and five other African countries. However, cost is incidental when the drugs aren't available. So-called 'stock-outs' have been the rule rather than the exception during the past five years, especially at small public clinics, says David Okumu, a doctor and an administrator at the Ugandan Ministry of Health who coordinates health services in Tororo.

Stock-outs began abruptly in 2005 when The Global Fund froze grants totalling US$201 million over allegations that some members of Uganda's Ministry of Health had misused the money. Although the funds were partially restored within a few months, and despite the fact that The Global Fund and the Ugandan government made arrangements to continue to supply vital drugs, many lives were lost. The supply chain for medicines like ACT “came to a halt”, says James Tibenderana, the African technical director of the Malaria Consortium, a non-profit organization that partners with international and local groups to control malaria in Africa and Asia. The African branch of the consortium is based in Kampala. “We essentially had no ACTs in the country in 2006 and 2007, and we were delayed with deploying insecticide-treated nets. We still have not recovered.” Even in the dry season, Uganda's lush lands provide plentiful ground for mosquitoes to breed. Credit: AMY MAXMEN The suspension of international funding can trigger tumultuous cascades in countries with frail infrastructure. When funds froze in 2005, for example, Uganda was gearing up to switch from cheaper, less effective antimalarials to ACTs. At the highest levels of the Ministry of Health, this switch meant that administrators had to draft lots of different documents — contracts with drug suppliers, reports to aid organizations, procurement plans and bidding documents — all to be discussed and signed. At the other end of the chain, vendors in cramped makeshift drug stores on dirt roads needed to be taught about the usage, price and storage of the new antimalarials. Each step requires manpower and money. And when logistics don't flow — as when the staff at large pharmacies have neither the time nor the training to predict demand and place appropriate orders — stock-outs occur. And because the drugs expire in a matter of months, they cannot be stockpiled. There are stories of ACTs going to waste in the relatively malaria-free southwestern regions of Uganda, while children in northern places like Tororo die for lack of medicines. Funding bottlenecks, inefficient procurement processes, transportation problems and inadequate stock keeping share the blame for the delay in introduction of ACTs for routine use — which did not happen in Uganda until 2008 (an advancement which regressed in 2009 with more nationwide stock-outs). Likewise, the latest first-line treatment for severe malaria recommended by the WHO is yet to reach the country. Before the Ugandan government can endorse this new intravenous therapy, which consists of the artemisinin derivative artesunate, it must ensure a steady supply chain and train hospital staff nationwide. In the meantime, doctors continue to treat severe malaria with intravenous quinine — a harsh substance that causes tinnitus, vomiting and vertigo, as well as increasing the risk of cardiac arrest. When Nature Outlook visited public and privately owned pharmacies in Tororo and Kampala in January 2012, ACTs were available. And according to an administrator at Tororo district hospital, they had been for a while. But Moses Kamya, head of the Department of Medicine at Makerere University College of Health Sciences in Kampala, predicts that stock-outs will happen again. As prices continue to drop, sales will rise and could exceed capacity. A big reason for this supply instability is that in Uganda, as in many African countries, privately owned pharmacies dispense ACTs to anyone who can pay for them, even without a prescription. One taxi driver in Kampala told Nature Outlook he swallows ACTs as a prophylaxis whenever he feels slightly sick. “Globally, we are in a precarious situation for ACTs,” says Sonali Korde, an advisor at the US President's Malaria Initiative based in Washington, DC. If countries mismanage their supplies or sell too many to people without the disease, she warns, stock-outs will happen and people will perish. Abandoned infirmaries Boosting the number and quality of staff in public healthcare would undoubtedly improve Uganda's situation. A shortage of doctors plagues much of sub-Saharan Africa. Uganda, like its neighbours Rwanda, Kenya, Ethiopia, the Democratic Republic of Congo (DRC) and Tanzania, has at most 1 doctor per 10,000 people, compared to 8 per 10,000 people in South Africa, 27 in both the US and UK, and 64 in Cuba. As a result, long waits for overwhelmed doctors often deter people from seeking medical help until it's too late. And village health workers, who deliver health education and occasionally malaria medicines, are unpaid volunteers in Uganda — as a result, Kamya says, these positions are often vacant. Some say the issue boils down to money. The son of peasants in western Uganda, Kakuru dreamed of being a doctor from a young age. He says he never tires of watching sick children recover. But he worries that the US$300 per month salary paid to public sector doctors will not be enough for him to provide a better quality of life for his young daughter than he himself experienced. “When we talk about a pay raise, the government just tells us that we have to love our nation,” Kakuru says. Many of his colleagues from medical school have left the country or joined non-governmental organizations (NGOs) that offer US$1,200 per month or more. “My friends have even taken NGO jobs in dangerous places like South Sudan if it means earning a better living,” he says. It is staff retention, not recruitment, that is Uganda's problem. “There are enough health workers trained in this country, but few stay in the public sector,” says Seraphine Adibaku, the malaria programme manager at the Ministry of Health. “You find healthcare facilities that are closed or struggling with very few staff,” he says. “The President has said that health is a priority area, but usually when it comes to sharing the annual budget, you find it falls short of what well-meaning leaders want to achieve.” Villagers travel to Tororo public hospital on foot, bicycle or boda-boda (left) where mothers and children wait in long queues to see a doctor. Credit: AMY MAXMEN Seeking sustainable answers Aid from international organizations is vital to malaria control. The Global Fund, which assembles donations from 54 governments, the Bill & Melinda Gates Foundation and other donors, has disbursed nearly US$162 million to Uganda to fight malaria since 2003. In addition, the US President's Malaria Initiative has given US$144 million since 2006. Aid has helped buy and distribute insecticide-treated bed nets and ACTs, educate villagers about malaria, train health workers, and spray homes in northern districts with insecticide. However, the projects don't include supplementing the salaries of doctors as an incentive for them to remain in the public sector. In other African countries, including Rwanda, The Global Fund provides salary 'top-ups' for doctors who meet performance criteria determined by its Ministry of Health. Yet the Ugandan government has not asked for this type of support, and The Global Fund has not provided it. Grants from international research institutions can enhance health infrastructure, although only indirectly. Fourteen years ago, Kamya collaborated with Phil Rosenthal, from the University of California, San Francisco, on a study funded by the WHO and the US National Institutes of Health (NIH); their efforts led to the formation of a non-profit organization called the Infectious Diseases Research Collaboration (IDRC). The IDRC now employs about 200 people, who help run clinical trials, studies and surveys in Uganda. Kamya says that patients who enrol in the trials receive quality care as well as health education, and the hospitals that host the research teams also benefit. “In Tororo, our doctors work as surgeons when they can, and we let the hospital use our generator when the lights go out during operations,” he says. Unfortunately, like the programmes operated by international organizations, grants for research projects must eventually end, often abandoning their local staff and patients. Still, past collaborations have created a cadre of trained investigators: a local resource that did not exist in Uganda when Kamya authored his first scientific paper in 1995. Kamya and other investigators now lead their own studies and train students year round. Nurturing local talent is important from more than simply a resource point of view. “We regularly share data with the Ministry of Health,” he says, “and hearing about the country's needs from a Ugandan is different than hearing about it from an American. Global problem; local solutions The global death toll from malaria is anywhere from 655,000 to 1.2 million (ref. 3). The reasons people die from this preventable and curable disease vary from region to region. Mountainous terrain in northeast India complicates the distribution of ACTs, whereas conflict in Burma, South Sudan and DRC has destroyed clinics where people might have gone for help. What is common to all the countries with a high incidence of malaria is that their people are poor and have inadequate access to education, drugs, diagnostic tests and doctors. Infrastructure improvements will be essential for malaria elimination, says Rob Newman, director of the Global Malaria Programme at the WHO — so if international aid lapses, health workers and hospitals will still be there. These systems aren't impossible to build, Newman says, but they do take long-term investments in human resources, logistics, regulation and surveillance. “Some people say that$6 billion is a lot of money, but I don't think it's an outrageous thing to ask for.”

According to the 2011 WHO World Malaria Report, malaria elimination will cost nearly US$4 billion more than the US$2 billion pledged (see 'The numbers game', page S14'). However, there are no new sources of funding on the horizon, so meeting this target before 2015 seems unlikely. “Some people say that $6 billion is a lot of money, but I don't think it's an outrageous thing to ask for,” Newman says. “Ask someone if they think a person should die because they can't afford a$5 bed net, a 50-cent diagnostic test and a \$1 drug.” Although sophisticated in their simplicity, these things mean nothing without practical ways to get them into the hands of mothers in distress.