Joel G. Breman

Bio: Joel G. Breman is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Developing country & Malaria. The author has an hindex of 35, co-authored 182 publications receiving 6929 citations.

The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden.

Abstract: Malarious patients experience asymptomatic parasitemia; acute febrile illness (with cerebral damage, anemia, respiratory distress, hypoglycemia); chronic debilitation (anemia, malnutrition, nervous system-related sequelae); and complications of pregnancy (anemia, low birth weight, increased infant mortality). These manifestations in patients, communities, and countries reflect intrinsic (human, parasite, mosquito) and extrinsic (environmental, social, behavioral, political, and economic conditions as well as disease-control efforts) determinants. At a minimum, between 700,000 and 2.7 million persons die yearly from malaria, over 75% of them African children. Between 400 and 900 million acute febrile episodes occur yearly in African children under 5 yr of age living in endemic areas. Although about half of these children are parasitemic, all merit consideration of malaria-specific therapy, which is becoming more problematic because of parasite resistance to drugs. These numbers will more than double over the next 20 yr without effective control. Fewer than 20% of these febrile episodes and deaths come to the attention of any formal health system. The relatively few ill patients who have any contact with the health services represent the "ears of the hippopotamus." Greatly intensified research activities and control of the intolerable burden of malaria are mandatory if economic development is to accelerate in Africa. In particular, support should be targeted to understanding and preventing malaria-induced anemia, hypoglycemia, effects on pregnancy, and neurologic and developmental impairment. To decrease and stop transmission of this intolerable scourge, there is an urgent need for malaria vaccines, newer drugs, and better vector control methods as well as the ability to improve current technologies and use them more efficiently.

Hemorrhagic Fever Viruses as Biological Weapons: Medical and Public Health Management

Abstract: ObjectiveTo develop consensus-based recommendations for measures to be taken by medical and public health professionals if hemorrhagic fever viruses (HFVs) are used as biological weapons against a civilian populationParticipantsThe Working Group on Civilian Biodefense included 26 representatives from academic medical centers, public health, military services, governmental agencies, and other emergency management institutionsEvidenceMEDLINE was searched from January 1966 to January 2002 Retrieved references, relevant material published prior to 1966, and additional sources identified by participants were reviewedConsensus ProcessThree formal drafts of the statement that synthesized information obtained in the evidence-gathering process were reviewed by the working group Each draft incorporated comments and judgments of the members All members approved the final draftConclusionsWeapons disseminating a number of HFVs could cause an outbreak of an undifferentiated febrile illness 2 to 21 days later, associated with clinical manifestations that could include rash, hemorrhagic diathesis, and shock The mode of transmission and clinical course would vary depending on the specific pathogen Diagnosis may be delayed given clinicians' unfamiliarity with these diseases, heterogeneous clinical presentation within an infected cohort, and lack of widely available diagnostic tests Initiation of ribavirin therapy in the early phases of illness may be useful in treatment of some of these viruses, although extensive experience is lacking There are no licensed vaccines to treat the diseases caused by HFVs

Conquering the Intolerable Burden of Malaria: What’s New, What’s Needed: A Summary

Abstract: Each year, up to three million deaths due to malaria and close to five billion episodes of clinical illness possibly meriting antimalarial therapy occur throughout the world, with Africa having more than 90% of this burden. Almost 3% of disability adjusted life years are due to malaria mortality globally, 10% in Africa. New information is presented in this supplement on malaria-related perinatal mortality, occurrence of human immunodeficiency virus in pregnancy, undernutrition, and neurologic, cognitive, and developmental sequelae. The entomologic determinants of transmission and uses of modeling for program planning and disease prediction and prevention are discussed. New data are presented from the Democratic Republic of the Congo, Tanzania, Ethiopia, and Zimbabwe on the increasing urban malaria problem and on epidemic malaria. Between 6% and 28% of the malaria burden may occur in cities, which comprise less than 2% of the African surface. Macroeconomic projections show that the costs are far greater than the costs of individual cases, with a substantial deleterious impact of malaria on schooling of patients, external investments into endemic countries, and tourism. Poor populations are at greatest risk; 58% of the cases occur in the poorest 20% of the world's population and these patients receive the worst care and have catastrophic economic consequences from their illness. This social vulnerability requires better understanding for improving deployment, access, quality, and use of effective interventions. Studies from Ghana and elsewhere indicate that for every patient with febrile illness assumed to be malaria seen in health facilities, 4-5 episodes occur in the community. Effective actions for malaria control mandate rational public policies; market forces, which often drive sales and use of drugs and other interventions, are unlikely to guarantee their use. Artemisinin-based combination therapy (ACT) for malaria is rapidly gaining acceptance as an effective approach for countering the spread and intensity of Plasmodium falciparum resistance to chloroquine, sulfadoxine/pyrimethamine, and other antimalarial drugs. Although costly, ACT ($1.20-2.50 per adult treatment) becomes more cost-effective as resistance to alternative drugs increases; early use of ACT may delay development of resistance to these drugs and prevent the medical toll associated with use of ineffective drugs. The burden of malaria in one district in Tanzania has not decreased since the primary health care approach replaced the vertical malaria control efforts of the 1960s. Despite decentralization, this situation resulted, in part, from weak district management capacity, poor coordination, inadequate monitoring, and lack of training of key staff. Experience in the Solomon Islands showed that spraying with DDT, use of insecticide-treated bed nets (ITNs), and health education were all associated with disease reduction. The use of nets permitted a reduction in DDT spraying, but could not replace it without an increased malaria incidence. Baseline data and reliable monitoring of key outcome indicators are needed to measure whether the ambitious goals for the control of malaria and other diseases has occurred. Such systems are being used for evidence-based decision making in Tanzania and several other countries. Baseline cluster sampling surveys in several countries across Africa indicate that only 53% of the children with febrile illness in malarious areas are being treated; chloroquine (CQ) is used 84% of the time, even where the drug may be ineffective. Insecticide-treated bed nets were used only 2% of the time by children less than five years of age. Progress in malaria vaccine research has been substantial over the past five years; 35 candidate malaria vaccines are in development, many of which are in clinical trials. Development of new vaccines and drugs has been the result of increased investments and formation of public-private partnerships. Before malaria vaccine becomes deployed, consideration must be given to disease burden, cost-effectiveness, financing, delivery systems, and approval by regulatory agencies. Key to evaluation of vaccine effectiveness will be collection and prompt analysis of epidemiologic information. Training of persons in every aspect of malaria research and control is essential for programs to succeed. The Multilateral Initiative on Malaria (MIM) is actively promoting research capacity strengthening and has established networks of institutions and scientists throughout the African continent, most of whom are now linked by modern information-sharing networks. Evidence over the past century is that successful control malaria programs have been linked to strong research activities. To ensure effective coordination and cooperation between the growing number of research and control coalitions forming in support of malaria activities, an umbrella group is needed. With continued support for scientists and control workers globally, particularly in low-income malarious countries, the long-deferred dream of malaria elimination can become a reality.

Poor-quality antimalarial drugs in southeast Asia and sub-Saharan Africa

Abstract: Poor-quality antimalarial drugs lead to drug resistance and inadequate treatment, which pose an urgent threat to vulnerable populations and jeopardise progress and investments in combating malaria. Emergence of artemisinin resistance or tolerance in Plasmodium falciparum on the Thailand-Cambodia border makes protection of the effectiveness of the drug supply imperative. We reviewed published and unpublished studies reporting chemical analyses and assessments of packaging of antimalarial drugs. Of 1437 samples of drugs in five classes from seven countries in southeast Asia, 497 (35%) failed chemical analysis, 423 (46%) of 919 failed packaging analysis, and 450 (36%) of 1260 were classified as falsified. In 21 surveys of drugs from six classes from 21 countries in sub-Saharan Africa, 796 (35%) of 2297 failed chemical analysis, 28 (36%) of 77 failed packaging analysis, and 79 (20%) of 389 were classified as falsified. Data were insufficient to identify the frequency of substandard (products resulting from poor manufacturing) antimalarial drugs, and packaging analysis data were scarce. Concurrent interventions and a multifaceted approach are needed to define and eliminate criminal production, distribution, and poor manufacturing of antimalarial drugs. Empowering of national medicine regulatory authorities to protect the global drug supply is more important than ever.

Diagnosis and management of smallpox

Abstract: The last case of endemic smallpox occurred in Somalia in 1977, and eradication of the disease was declared in 1980. With no natural reservoir, variola virus, which causes smallpox, has existed only in laboratories; indeed, the last case of smallpox was due to infection acquired in a laboratory in the United Kingdom in 1978. During the global program of smallpox eradication, the World Health Organization (WHO) made concerted efforts to decrease the number of laboratories retaining variola virus. On the basis of contacts with all countries and a total of 823 microbiology institutions, 76 such laboratories had been identified by . . .

Genome sequence of the human malaria parasite Plasmodium falciparum

Abstract: The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host-parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria.

Leishmaniasis Worldwide and Global Estimates of Its Incidence

Abstract: As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence. Mortality data were extremely sparse and generally represent hospital-based deaths only. Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year. Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis. These data should help to define control strategies and reinforce leishmaniasis advocacy. Funding: The Spanish Agency for International Cooperation for Development (AECID) has provided generous support to the WHO Leishmaniasis program since 2005. This support permitted among many other activities regional meetings with the AFRO, EURO, PAHO and SEARO countries, and provided for short term contracts for IDV, MdB, MH and JS related to the preparation of the country profiles. Sanofi provided a grant for a regional meeting with the EMRO countries and various activities related to the control of cutaneous Leishmaniasis in the EMRO region. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: alvarj@who.int . These authors contributed equally to this work " For a full list of the members of the WHO Leishmaniasis Control Team please see the Acknowledgments section.