Mortality trends among refugees in Honduras, 1984-1987.

Mortality data collected from 1984 to 1987 through a routine standardized health information system in the five main refugee populations of Honduras were reviewed. The direct standardized mean annual death rate for all refugees was 5.5 per 1000 population (Honduras population as reference; Honduras mortality rate: 10.1 per 1000). Mortality decreased or remained stable among Salvadoran refugees from 1984 to 1987, but increased among Nicaraguan refugees after 1985. The highest neonatal (56.1 per 1000 livebirths), infant (126.1 per 1000 livebirths) and under-five-year-olds (35.7 per 1000 child less than five years of age) mortality rates were observed in the two Nicaraguan camps. These two camps had the highest rate of newly arriving refugees. Deaths in infants and under-five-year-olds accounted for 42 and 54.1% of all deaths respectively. Of all deaths under five years of age, respiratory infections, diarrhoeal diseases and measles accounted for 21.4%, 22.1% and 4.7%, respectively. Mortality rates, particularly among under-five-year-olds and infants increased when the rate of newly arriving refugees was higher. The importance of adapted health surveillance in refugee settlements is discussed.

Permethrin-impregnated bed nets for the prevention of malaria in schoolchildren on the Thai-Burmese border.

A double-blind controlled trial was undertaken from August 1990 to February 1991 among Karen children on the Thai-Burmese border to evaluate the effects on malaria incidence and prevalence of permethrin-treated bed nets. Three hundred and fifty schoolchildren, aged 4 to 15 years, were allocated at random to receive either a permethrin-impregnated net or a non-treated net. The incidence of malaria infections, confirmed by a blood film, was assessed during 6 months. Three surveys were conducted, on admission and 3 and 6 months later, to measure the prevalence of infections and spleen rates. Compliance was assessed by monthly home visiting. The use of permethrin-treated bed nets reduced the number of parasitaemic Plasmodium falciparum infections by 38% and the number of symptomatic episodes by 42%. The number of P. vivax malaria attacks was similar in each group. The prevalence of positive blood films in the 2 groups did not change significantly during the study. A reduction in spleen rate by 50% in both groups at the end of the study period could not be related to the overall use of nets. Compliance was high and no side-effect was reported. The long-term effects on morbidity and mortality need to be assessed after distribution of permethrin treated bed nets at the village level.

Malaria surveillance among the displaced Karen population in Thailand April 1984 to February 1989, Mae Sot, Thailand.

Right from the arrival of the displaced Karen people in Thailand, Médecins sans Frontières (MSF) identified malaria as the top priority problem. A program of patient care based on the coupled laboratory/dispensary was set up in April 1984. Immediately a system of surveillance of morbidity and mortality from malaria was set up. This study consisted of analysing data gathered over a period of five years. During this time, the displaced population increased from 9,000 to 20,000. Analysis of the trends shows a hyperendemic situation with an annual incidence rate of 1,067 per thousand in 1984. This figure was 600 per thousand in 1988. 1,500 blood smears were checked each month and the positive predictive value of clinical suspicion was 45% on average. Plasmodium falciparum represented 80% of infections. The malaria case fatality ratio over the course of the last two years of surveillance was 0.3%. Five years observation show that the fight against malaria in this region can be based on the development of curative services and laboratories.

[Drugs for 'neglected diseases': a bitter pill]. / Medicijnen voor 'verwaarloosde ziekten': een bittere pil.

Neglected diseases are diseases restricted to poor areas; diseases for which there exist no commercial incentives to invest in the development of new treatments. Patients suffering from these diseases often have no access to essential drugs; this can be a matter of life and death. Lack of research and patent protection play a crucial role. Both are cost driven; greed in the West curtails the availability of life-saving drugs for all. Treatment options for trypanosomiasis and visceral leishmaniasis are lacking. It is recommended that drugs for the treatment of 'neglected diseases' be developed via a centralised, public approach that is not based on profit, rather than leaving it to free enterprise.

[Risk factors for malnutrition in 0-59-month-old infants in 2 districts of Niger]. / Facteurs de risque de la malnutrition chez les enfants de 0-59 mois dans deux arrondissements au Niger.

A nutritional survey by cluster sampling at 2 degrees, carried out in April 1987 within a range of action of 6 health structures in Niger, has permitted the calculation of the weight/height index among children aged from 0 to 59 months and the malnutrition rate, according to the socio-economic status, the demographic variables, the intercurrent diseases, the use of health departments, alimentary and weaning habits. The standardized rate of acute malnutrition for the age among of 0-59 months is 12.3%. The risk factors for acute malnutrition retained after logistical regression are the age groups of 6-17 months and 18-29 months, the areas of Guidan Roumdji, Tahoua, Tajae, Guidan Sori and the group of children that have contracted diarrhea during the 15 days preceding the survey.

Efficacy of a therapeutic feeding centre evaluated during hospitalization and a follow-up period, Tahoua, Niger, 1987-1988.

Between 1 February 1987 and 31 May 1988 an evaluation of a nutritional rehabilitation centre in Tahoua, Niger was conducted. Among the 381 children admitted to the centre, 61 (16%) had kwashiorkor and 347 (91.3%) were aged between 6 and 29 months. Recovery and death rates were 46.2% and 14.4%, respectively. The median duration of stay until recovery was 21 days. Sixty-two per cent of deaths occurred during the 1st week of hospitalization. Three risk factors for death were identified by the study: patients with kwashiorkor with a weight/height (W/H) less than -3 SD, those with marasmus with a W/H less than -5 SD, and those dehydrated with marasmus. Among children included in the follow-up study after leaving the centre, the risk of dying during the follow-up period among children who absconded was 7.1 times higher than the risk observed among children who recovered. Among the children who recovered, no relapse was observed 3-18 months after they left the centre. This investigation indicates the importance of intensive therapeutic feeding centres in areas with a high prevalence of malnutrition.

Is orphan drug status beneficial to tropical disease control? Comparison of the American and future European orphan drug acts.

UNLABELLED: OBJECTIVES To quantify past outcomes of tropical pharmacology research and development (R & D) and to assess past benefits of the American orphan drug act and potential benefits of the future European orphan drug regulation on tropical diseases. METHODS: This paper presents two analyses: a 1983-97 retrospective study of the United States Orphan Drug Act concerning rare diseases and a prospective study of the European Proposal for a Regulation Concerning Orphan Drugs and its possible impact on tropical diseases. RESULTS: Different programmes have in the past tried to stimulate R & D in this area, but results remain limited. Of 1450 new chemical entities marketed between 1972 and 1997, 13 were specifically for tropical diseases and considered as essential drugs. Between 1983 & 1997, the US Orphan Drug Act approved 837 drugs and marketing of 152 new molecular entities (NMEs). Three NMEs have been designated for malaria and human African trypanosomiasis. Seven others, already commonly used in tropical diseases, received either orphan designation or an orphan approval for another indication. Pharmaceutical companies benefit from the US framework only when the US market exclusivity clause was applicable. Future European orphan drug regulation appears to be similar to the US Orphan Drug Act. CONCLUSION The orphan drug programmes relating to rare diseases have met with some success. Considering tropical diseases rare diseases seems inadequate to boost pharmaceutical R & D. However, some provisions of the European text may be relevant to tropical diseases, admitting the need for a more specific rule for evaluations of this kind of drug and recognizing the existence of 'diseases of exception'.

Access to essential drugs in poor countries: a lost battle?

Drugs offer a simple, cost-effective solution to many health problems, provided they are available, affordable, and properly used. However, effective treatment is lacking in poor countries for many diseases, including African trypanosomiasis, Shigella dysentery, leishmaniasis, tuberculosis, and bacterial meningitis. Treatment may be precluded because no effective drug exists, it is too expensive, or it has been withdrawn from the market. Moreover, research and development in tropical diseases have come to a near standstill. This article focuses on the problems of access to quality drugs for the treatment of diseases that predominantly affect the developing world: (1) poor-quality and counterfeit drugs; (2) lack of availability of essential drugs due to fluctuating production or prohibitive cost; (3) need to develop field-based drug research to determine optimum utilization and remotivate research and development for new drugs for the developing world; and (4) potential consequences of recent World Trade Organization agreements on the availability of old and new drugs. These problems are not independent and unrelated but are a result of the fundamental nature of the pharmaceutical market and the way it is regulated.

Drugs for neglected diseases: a failure of the market and a public health failure?

Infectious diseases cause the suffering of hundreds of millions of people, especially in tropical and subtropical areas. Effective, affordable and easy-to-use medicines to fight these diseases are nearly absent. Although science and technology are sufficiently advanced to provide the necessary medicines, very few new drugs are being developed. However, drug discovery is not the major bottleneck. Today's R&D-based pharmaceutical industry is reluctant to invest in the development of drugs to treat the major diseases of the poor, because return on investment cannot be guaranteed. With national and international politics supporting a free market-based world order, financial opportunities rather than global health needs guide the direction of new drug development. Can we accept that the dearth of effective drugs for diseases that mainly affect the poor is simply the sad but inevitable consequence of a global market economy? Or is it a massive public health failure, and a failure to direct economic development for the benefit of society? An urgent reorientation of priorities in drug development and health policy is needed. The pharmaceutical industry must contribute to this effort, but national and international policies need to direct the global economy to address the true health needs of society. This requires political will, a strong commitment to prioritize health considerations over economic interests, and the enforcement of regulations and other mechanisms to stimulate essential drug development. New and creative strategies involving both the public and the private sector are needed to ensure that affordable medicines for today's neglected diseases are developed. Priority action areas include advocating an essential medicines R&D agenda, capacity-building in and technology transfer to developing countries, elaborating an adapted legal and regulatory framework, prioritizing funding for essential drug development and securing availability, accessibility, distribution and rational use of these drugs.

Availability and affordability of treatment for Human African Trypanosomiasis.

Human African Trypanosomiasis (HAT) is a re-emerging disease whose usual treatments are becoming less efficient because of the increasing parasite resistance. Availability of HAT drugs is poor and their production in danger because of technical, ecological and economic constraints. In view of this dramatic situation, a network involving experts from NGOs, WHO and pharmaceutical producers was commissioned with updating estimates of need for each HAT drug for the coming years; negotiations with potential producers of new drugs such as eflornithine; securing sustainable manufacturing of existing drugs; clinical research into new combinations of these drugs for first and second-line treatments; centralizing drug purchases and their distribution through a unique non-profit entity; and addressing regulatory and legal issues concerning new drugs.

Long-acting chloramphenicol versus intravenous ampicillin for treatment of bacterial meningitis.

In most developing countries, bacterial meningitis (BM) is associated with a high case-fatality rate. The search for a simple, convenient, and inexpensive antibiotic treatment remains a priority. In this study, a non-blinded, multicentre, randomised clinical trial of 528 cases of BM was done in two hospitals in Mali and Niger, between March, 1989, and May, 1990, to see whether a double injection of long-acting chloramphenicol (on admission to hospital and 48 h later) is as effective as a course of intravenous ampicillin (8 days, 4 times a day). The cumulative case-fatality rate on day 4 (principal end-point) among the chloramphenicol (254 patients) and ampicillin (274) groups were, respectively, 28% and 24.5% (relative risk 1.14, 95% confidence interval 0.86-1.52). No outbreak occurred during the study period. The hospital case-fatality rate was 33.1%. Main risk factors for death were associated with clinical condition on admission--ie, altered consciousness, convulsions, or dehydration. The case-fatality rates were 13% (21/161) for Neisseria meningitidis, 36.1% (48/133) for Haemophilus influenzae, and 67% (77/115) for Streptococcus pneumoniae. In a multiple logistic regression model, controlling for the differential distribution of potential risk factors (including bacterial species), there was no difference between treatment groups. Our findings suggest that long-acting chloramphenicol is a useful first-line presumptive treatment for BM in high-incidence countries.