Indonesia’s rate of human deaths from avian influenza rose by at least 20% between 2005 and 2007 despite heightened control efforts, according to research¹ published in The Lancet.

“H5N1 case fatality rates in Indonesia have increased… even though case management protocols, surveillance, and equipment across the country have improved since 2005,” write Nyoman Kandun and colleagues from the Indonesian Ministry of Health. “The case-fatality rate from 2005 to 2008 increased from 65.0% in 2005… to 86.8% in 2007.”

Their research also suggests that delays in receiving drugs to treat infections with the H5N1 virus can reduce patients' already slim chances of surviving the disease by up to half. Experts find the Indonesian data on bird flu cases to be limited, but say that some lessons can be learned from the country’s experience.

Indonesia is home to over a third of all human avian influenza cases reported worldwide. As of 19 June this year, the country has seen 135 cases of which 110 have been fatal, according to the World Health Organisation. Despite stepping up prevention and surveillance measures in 2002, infection rates continue to soar, making Indonesia a likely place for the emergence of a bird flu strain that is able to spread easily between people and spark a pandemic.

Looking to pinpoint factors associated with fatality in H5N1-infected people, Kandun and colleagues analysed data from the 127 cases of avian influenza recorded in the country between June 2005 and February 2008. The data came from interviews held with bird flu patients, their families, and health workers who treated them.

Between 2005 and 2007, the fatality rate of human infection jumped by more than 20%, say the team, reaching over 85%. The rate has now nudged down to 81%, according to data covering the months of January and February 2008. People were less likely to die from the infection if their case was linked to a cluster, as opposed to an isolated incident, add the authors.

The chances of survival improved if patients received treatment with oseltamivir at an early stage of the disease. When given the drug within two to four days of becoming infected, nearly double the number of people survived, compared with those who didn’t start treatment until seven days or later, say Kandun and colleagues.

In an associated article², Shelia Bird and Jeremy Farrar, of the UK Medical Research Council Biostatistics Unit in Cambridge, raise questions about the completeness of data used in the study and the methods used to analyse them. More precise evidence could enhance the lessons learned from Indonesia’s human cases, note Bird and Farrar, adding that a detailed description of the data has not been disclosed.

“Inferences [from the study] about emerging infections are initially uncertain,” they warn. “National protocols for a novel disease carry a risk that, inadvertently, a wrong standard will be adopted which we will learn about only with hindsight, by serendipity, via international comparisons, or from randomised trials.”

Important questions that the study leaves unanswered include whether patients belonging to groups or ‘clusters’ were all infected at the same time, and whether the disease progressed in a similar way among people in these clusters. Kandun et al. admit that Indonesia’s definition of a H5N1 cluster is “strict”, and that this may have influenced their results.

“There is a clear need to identify definite causes for high case-fatality,” say Kandun and colleagues. But Bird and Farrar suggest different priorities for Indonesia. The country has a crucial role to play in the world’s response to a potentially devastating H5N1 pandemic, they explain.

Tightened and more precise surveillance alongside monitoring of confirmed and suspected human cases of infection, as well as people who test negative, will allow better global understanding of the disease. This is an area where Indonesia can take the lead, say Bird and Farrar.

The commercial exchange of human organs should be banned with the support of transplant professionals, national laws, and international guidelines, according to a declaration published in the Clinical Journal of the American Society of Nephrology.

“The Istanbul Declaration proclaims that the poor who sell their organs are being exploited, whether by richer people within their own countries or by transplant tourists from abroad,” write participants of a summit convened by the International Society of Nephrology. “Moreover, transplant tourists risk physical harm by unregulated and illegal transplantation.”

Reflecting views of more than 150 professionals, the text of the Declaration was finalised last spring in Istanbul, Turkey. Experts say the document offers practical steps to reduce cross-border commercial organ transplantation, but there are ‘players’ missing from the table.

The decades-old problem of organ trafficking and transplant tourism has become more prominent with the advent of new communication technologies and ease of travel. The practice puts the health of donors and recipients at risk, according to the article, and takes advantage of the world’s poorest and most vulnerable people.

Done lawfully and safely, organ donation and transplantation can be life-saving solutions to serious health problems. But a shortage of available organs worldwide has created a ‘market’ for their sale across borders. The demand is often met by richer “patient-tourists”, according to the article. “For example, as of 2006, foreigners received two-thirds of the 2000 kidney transplants performed annually in Pakistan,” write the authors.

Corrupt traffickers are also fuelling the rise in the commercial trade of organs, according to the World Health Organization. These ‘brokers’ make a large profit, often passing on to donors less than 1% of the money they receive for organising a transplant.

A resolution passed by the WHO in 2004 urged countries to protect people victimised by these practices. But in light of what they see as a growing and urgent problem that threatens the legacy of transplantation, the Summit participants set forth proposals and principles that build on the Universal Declaration of Human Rights. These will be presented to national health authorities and organisations for consideration.

“The [Istanbul] Declaration should reinforce the resolve of governments and international organisations to develop laws and guidelines to bring an end to wrongful practices,” write the authors. “The broad representation at the Istanbul Summit reflects the importance of international collaboration and global consensus to improve donation and transplantation practices.”

The document lays out principles that range from prevention of organ failure, in order to increase their availability, to the provision of the best possible health care for both donors and recipients of a transplant organ. Countries should improve treatment of patients with serious chronic diseases to minimise the need for new organs, it says. But when transplant is needed, national programmes must ensure that this is done according to international standards and that sharing of organs is equitable.

Leigh Turner, Associate Professor at the Center for Bioethics and School of Public Health at the University of Minnesota, USA, says that the Declaration offers several practical steps that might lead to a reduction in cross-border commercial organ transplantation. But putting laws into practice is often the bigger problem with legislation that prohibits organ trafficking, he points out.

“In many instances an absence of legislation is not what permits commercial sale of organs,” Turner explains. “Rather, organ trafficking occurs because of corruption in law enforcement agencies, government ministries and hospitals.”

Commercial organ transplants occur regularly in certain places where the sale of organs is outlawed, he says. But the paper leaves unanswered questions as to how the laws put forward should be enforced, and who should administer penalties for those people who promote illegal practices.

“Serious efforts to combat organ trafficking need to get law enforcement officials more involved,” says Turner. “It’s the classic problem with legislation and prohibitions — they don’t enforce themselves.”

Many countries in south-eastern Europe where Crimean–Congo haemorrhagic fever (CCHF) is endemic have seen a record number of infections in 2008, reports the World Health Organization’s Regional Office for Europe (WHO/Europe). But the worst is yet to come, it warns.

“Data available for 2008 indicate CCHF virus is circulating with particular intensity in Turkey, the Balkans, and southern districts of the Russian Federation,” writes WHO/Europe online. “The period during which transmission is highest is late spring–summer… The number of suspected or confirmed cases in these endemic zones is therefore highly likely to increase in the coming weeks.”

CCHF is a virus carried by ticks that live in semi-desert regions. The ticks can infect cattle, and most human cases of the disease occur among farmers or other people who come into contact with livestock. Symptoms usually appear one to nine days after a tick bite, and include fever, muscle pain, dizziness, and sensitivity to light.

In the past, as many as 40–50% of people infected with the CCHF virus died during epidemics in resource-poor settings, according to the report. In some instances, healthcare workers have caught the disease from their patients. The latest trends were revealed with data compiled by EpiSouth, a collaborative project aiming to improve infectious disease surveillance in Europe.

“CCHF intensified activity and outbreaks constitute a threat to public health services because of its high case fatality ratio, its potential for nosocomial transmission, and the difficulties in case management and prevention requiring a sustained multi-sectoral approach,” says WHO/Europe.

In Turkey, the CCHF virus has recently re-emerged on a much larger scale since it was first detected over 30 years ago. “This could be due to the multiplication of vectors and reservoir animals in rural areas,” notes WHO/Europe in the report. “Temperature changes may also play a role.”

Turkey’s first human symptomatic case of CCHF appeared in 2002, and the number of cases has increased year on year. In 2008, an epidemic is underway that has the highest fatality rate ever seen in the country, with nearly 690 cases confirmed so far. By comparison, just 17 cases were reported in 2002.

In the Russian Federation, infections with the virus have also been rising steadily since 2002 and the death rate has almost doubled in that same period. In June this year, Greece confirmed its first symptomatic case of CCHF infection in a female farmer who subsequently died.

Although the number of infections and fatalities in Turkey and the Russian Federation has risen over the past six years, fewer people are dying from the disease compared with previous epidemics seen in CCHF-prone countries. “This is due to the quality of diagnostic and medical management of cases, and to a sensitive system of detection through systematic screening of people referred for tick bites in endemic areas,” says WHO/Europe.

Other areas of Europe affected by CCHF are Kosovo, Albania, and Bulgaria. Simple precautions such as using repellents and wearing longer clothing can prevent tick bites, add the authors. Removing ticks carefully with forceps can also help to prevent infection with the virus.

The USA has issued updated guidelines for the prevention of malaria in refugees entering the country, in the American Journal of Tropical Medicine and Hygiene this month. They replace those recommended in 1999, in light of rising numbers of displaced people arriving in the USA from malaria-endemic zones.

“The revised regime for pre-departure presumptive treatment [for malaria in refugees arriving from sub-Saharan Africa] is artesinin-based combination therapy (ACT),” write William Stauffer and colleagues. “The currently recommended ACT regime is artemether-lumefantrine because it is available as a fixed combination tablet, is available in most refugee camp settings, has a wide therapeutic window, has a minimal adverse event profile, and is consistent with most national guidelines for treating clinical malaria.”

Every year up to 70,000 refugees are granted asylum in the USA. Among them are a rising number of people from sub-Saharan Africa. The proportion of refugees from this region entering the USA rose by 30% between 1998 and 2005. These new populations bring with them new patterns of infection and disease, including severe malaria caused by the Plasmodium falciparum parasite, which is endemic in much of sub-Saharan Africa.

In malaria-endemic areas, displaced people living in temporary refugee camps shoulder a high burden of malaria. In some cases, the parasite enters the body but does not cause disease for weeks or months. Once refugees arrive in the USA, these subclinical infections can develop into malaria, often going unnoticed or mistreated by doctors who are unfamiliar with the disease, resulting in death, according to Stauffer et al. Untreated malarial infection can also spark localised transmission of the disease, making it a public health concern.

“Furthermore, malarial illness may interfere with a refugee’s successful integration into a host community because of issues such as physical incapacity, added financial stresses, and social stigmatization,” write the authors.

Since 1999, the US Centers for Disease Control and Prevention have recommended that refugees from sub-Saharan Africa take presumptive anti-malarial therapy in the form of sulfadoxine-pyrimethamine before they leave their country of origin or asylum. Recent studies have suggested that although this has been associated with a reduction in the number of infections with the P. falciparum parasite for some groups of African refugees, the infection still persists in many.

“This could be caused by several factors including resistance of the parasite to [sulfadoxine-pyrimethamine], failure to receive medication, poor drug absorption, and/or re-infection after treatment before departure,” note the authors.

Under the new recommendations, medical professionals should administer and watch patients taking the artemisinin-based combination therapy six times over three days, and the course should be completed no sooner than three days before departure, say the team. People who cannot take the medication, such as pregnant or breastfeeding women, and children that weigh under 5 kg, should be screened for the malaria parasite before they leave for the USA and then monitored for three months on arrival. No presumptive treatment is currently recommended for refugees relocating from other parts of the world, they add.

“These recommendations are put forth in an attempt to decrease potential malaria-related morbidity and mortality among refugees resettling to the United States, facilitate successful integration of refugees into host communities, decrease public health risk to the US population, and decrease the costs to host communities,” write the authors.

It takes little effort to add a level of detail to geographical models to improve how accurately areas with high lead exposure are spotted, environmental scientists report. This shows that better prediction of at-risk populations is a practical option and could boost prevention efforts, they suggest, as long as the digital data needed are available. 

“This study demonstrates the feasibility of widespread replication of highly spatially resolved [detailed] childhood lead exposure risk models,” write Dohyeong Kim and colleagues online in Environmental Health Perspectives. “The models performed well enough to identify high-risk areas for targeted intervention, even with a relatively low level of effort on geocoding [linking data with geographical locations].”

A previous study by the same research group revealed a dramatic increase in the proportion of children identified as high risk for lead poisoning when models were built with finer geographical detail. Now they pin down just how much time and effort it takes to introduce different levels of detail, and to produce better predictions.

The study included information from just one US state. But as electronic data become cheaper to store and simpler to handle, predictive models built elsewhere could also bolster efforts to protect children from lead exposure, say the authors.

“The models guide resource-constrained local health and housing departments and community-based organizations on how best to expand their efforts in preventing and mitigating lead exposure in their communities,” Kim et al. point out.

Lead was phased out of environmental sources as US pollution regulations kicked in around the late 1970s. Although human exposures to the toxic metal are now lower as a result, recent evidence suggests that children might be harmed by exposures below 10 µg/dl — the CDC-specified level of blood lead that triggers concern.

In the USA, more than 500,000 children aged six or younger have exceeded this ‘action’ level in recent years, according to the authors. Children born outside the country or living in poor parts of the world can experience higher exposures that raise the risk to health.

Working with data from 18 diverse counties in North Carolina, Kim and colleagues collected over 467,000 blood test results for 336,736 children. These were combined with demographic data from the 2000 US Census at the lowest level of geographical detail provided. But the authors zoomed into more precise locations by using data on ‘residential tax parcels’, which generally cover single-family or multi-family housing.

They linked data on blood lead and location in three ways, which represented different levels of time and effort for an employee. ‘Level I’ took seven to nine days for one member of staff working an eight-hour day, ‘Level II’ took 20 days, and ‘Level III’ took an extra three to four months. Spending more time meant that more records could be added to a statistical model used to predict areas of high risk from exposures related to housing only.

“The lead exposure risk model based on Level I and II geocoding performs on par with the model based on all three levels of geocoding, with considerably less effort expended on developing the model,” report Kim et al. “Additional time and resources dedicated to Level III geocoding do not significantly alter or impact statistical modeling results.”

The results show promise for a system that helps health professionals to reach more people and prioritise areas for intervention based on lead risk, say the authors. By adding data on recent births, they could also target families with young children before these reach an age when higher exposures tend to occur.