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Populations affected by armed conflict have experienced severe public health consequences mediated by population displacement, food scarcity, and the collapse of basic health services, giving rise to the term complex humanitarian emergencies. These public health effects have been most severe in underdeveloped countries in Africa, Asia, and Latin America. Refugees and internally displaced persons have experienced high mortality rates during the period immediately following their migration. In Africa, crude mortality rates have been as high as 80 times baseline rates. The most common causes of death have been diarrheal diseases, measles, acute respiratory infections, and malaria. High prevalences of acute malnutrition have contributed to high case fatality rates. In conflict-affected European countries, such as the former Yugoslavia, Georgia, Azerbaijan, and Chechnya, war-related injuries have been the most common cause of death among civilian populations; however, increased incidence of communicable diseases, neonatal health problems, and nutritional deficiencies (especially among the elderly) have been documented. The most effective measures to prevent mortality and morbidity in complex emergencies include protection from violence; the provision of adequate food rations, clean water and sanitation; diarrheal disease control; measles immunization; maternal and child health care, including the case management of common endemic communicable diseases; and selective feeding programs, when indicated.
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PMID:The public health aspects of complex emergencies and refugee situations. 914 21

Malaria remains an overwhelming problem in tropical developing countries, with 300 to 500 million new cases and 1.5 to 3.5 million deaths per year. Malaria is a potentially life-threatening disease for travelers to the tropics. Imported malaria is an important clinical problem in nonendemic areas of the world because of increasing numbers of travelers, overseas workers, and immigrants from endemic areas. According to the World Health Organization's criteria, the recognition of one or more of the following clinical features should raise the suspicion of severe malaria: cerebral malaria (unrousable coma), severe anemia (hemoglobin <5 g/dL), renal failure (serum creatinine >3 mg/dL), pulmonary edema or adult respiratory distress syndrome, hypoglycemia (glucose <40 mg/dL), circulatory collapse or shock, disseminated intravascular coagulation, repeated generalized convulsions, acidosis (pH <7.25), macroscopic hemoglobinuria, hyperparasitemia (>5 percent of the erythrocytes infested by parasites), or jaundice (bilirubin >3 mg/dL). Although only a small proportion of patients with malaria develops severe manifestations, these patients require the most urgent and intensive care. Mortality among patients with cerebral malaria, even when treated in modern intensive care units, exceeds 30%, and when complicated by the adult respiratory distress syndrome, it may approach 80%. Among travelers, mortality remains a serious issue because of failure to obtain and use preventive measures, delay in seeking medical attention, and misdiagnosis.
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PMID:Imported severe falciparum malaria in Israel. 977 25

A combination of atovaquone and proguanil has been found to be quite effective in treating malaria, with little evidence of the emergence of resistance when atovaquone was used as a single agent. We have examined possible mechanisms for the synergy between these two drugs. While proguanil by itself had no effect on electron transport or mitochondrial membrane potential (DeltaPsim), it significantly enhanced the ability of atovaquone to collapse DeltaPsim when used in combination. This enhancement was observed at pharmacologically achievable doses. Proguanil acted as a biguanide rather than as its metabolite cycloguanil (a parasite dihydrofolate reductase [DHFR] inhibitor) to enhance the atovaquone effect; another DHFR inhibitor, pyrimethamine, also had no enhancing effect. Proguanil-mediated enhancement was specific for atovaquone, since the effects of other mitochondrial electron transport inhibitors, such as myxothiazole and antimycin, were not altered by inclusion of proguanil. Surprisingly, proguanil did not enhance the ability of atovaquone to inhibit mitochondrial electron transport in malaria parasites. These results suggest that proguanil in its prodrug form acts in synergy with atovaquone by lowering the effective concentration at which atovaquone collapses DeltaPsim in malaria parasites. This could explain the paradoxical success of the atovaquone-proguanil combination even in regions where proguanil alone is ineffective due to resistance. The results also suggest that the atovaquone-proguanil combination may act as a site-specific uncoupler of parasite mitochondria in a selective manner.
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PMID:A mechanism for the synergistic antimalarial action of atovaquone and proguanil. 1034 48

Atovaquone represents a class of antimicrobial agents with a broad-spectrum activity against various parasitic infections, including malaria, toxoplasmosis and Pneumocystis pneumonia. In malaria parasites, atovaquone inhibits mitochondrial electron transport at the level of the cytochrome bc1 complex and collapses mitochondrial membrane potential. In addition, this drug is unique in being selectively toxic to parasite mitochondria without affecting the host mitochondrial functions. A better understanding of the structural basis for the selective toxicity of atovaquone could help in designing drugs against infections caused by mitochondria-containing parasites. To that end, we derived nine independent atovaquone-resistant malaria parasite lines by suboptimal treatment of mice infected with Plasmodium yoelii; these mutants exhibited resistance to atovaquone-mediated collapse of mitochondrial membrane potential as well as inhibition of electron transport. The mutants were also resistant to the synergistic effects of atovaquone/ proguanil combination. Sequencing of the mitochondrially encoded cytochrome b gene placed these mutants into four categories, three with single amino acid changes and one with two adjacent amino acid changes. Of the 12 nucleotide changes seen in the nine independently derived mutants 11 replaced A:T basepairs with G:C basepairs, possibly because of reactive oxygen species resulting from atovaquone treatment. Visualization of the resistance-conferring amino acid positions on the recently solved crystal structure of the vertebrate cytochrome bc1 complex revealed a discrete cavity in which subtle variations in hydrophobicity and volume of the amino acid side-chains may determine atovaquone-binding affinity, and thereby selective toxicity. These structural insights may prove useful in designing agents that selectively affect cytochrome bc1 functions in a wide range of eukaryotic pathogens.
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PMID:Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites. 1044 80

Carboxylic true ionophores were previously demonstrated to have efficient antimalarial activity against the human parasite Plasmodium falciparum, with a 50% inhibitory concentration around nM and generally high selectivity as compared to their toxic effects against mammalian cell lines. The decreased molecular packing of the erythrocyte membrane outer leaflet after malarial infection could explain the preferential ionophore interaction with infected erythrocytes. Monolayer penetration experiments using different phospholipid films showed strong incorporation of true carboxylic ionophores, from classes 1 (nigericin) and 2 (lasalocid), up to a surface pressure close to film collapse. The interaction was slightly higher with PC (phosphatidylcholine) monolayers than with monolayers composed of cholesterol-containing total lipid extracts from either malaria-infected or normal erythrocytes, and the two latter induced identical interactions with 5-bromo lasalocid. Surface pressure-area isotherms for pure ionophores on water and surface tension of ionophore aqueous solutions clearly highlighted the surface-active characteristics of these ionophores and allowed determination of their molecular area in compact monolayers. The estimated ionophore concentration in the mixed interfacial layers indicates that higher amounts (threefold more) of ionophores might be integrated in infected erythrocyte membrane due to their impaired molecular packing as compared to normal erythrocytes. This infection-enhanced penetration efficiency does not appear directly related to the change in erythrocyte membrane lipid composition, but it could be the basis of ionophore selectivity for infected erythrocytes. Copyright 1999 Academic Press.
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PMID:Ionophore-Phospholipid Interactions in Langmuir Films in Relation to Ionophore Selectivity toward Plasmodium-Infected Erythrocytes. 1050 69

This article highlights the crisis experienced in the beleaguered Democratic Republic of Congo (DRC). The peace talks to be conducted beginning January 20, 2000, will focus on the near-total collapse of health services and the impending humanitarian megacatastrophe in the country. The two civil wars for the past decades have resulted in an essentially bankrupt health sector and a widespread inaccessibility of basic health care. On December 1999, the UN Security Council president described the situation as the major challenge facing Africa, the UN, and the international community. Reports continue of outbreaks of epidemic infections, including vaccine-preventable diseases and hemorrhagic fevers, and unchecked diseases such AIDS, malaria, and sleeping sickness. On the other hand, the chronic malnutrition rate was reported to be as high as 31%, with some cities on the brink of famine. In addition, life expectancy has fallen by 5 years and maternal mortality has doubled, with hundreds of thousands of displaced people in refugee camps unable to sustain themselves. The meeting on January 10, 2000, will tackle the AIDS epidemic in Africa, and the DRC will be the major test of this policy, since its infection rate reached 4.35% in 1997. The withdrawal of international cooperation, which was blamed for worsening the situation, was refuted by another author stating that war and political violence killed the people.
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PMID:Agency warns of crisis in beleaguered Democratic Republic of Congo. 1067 31

Malaria has been existing in Armenia since antiquity. In the 1920"s to 1930s, thousands of people suffered from this disease in the country. Enormous efforts were required to prevent further spread of the disease. A network was set up, which consisted of a research institute and stations. A total of 200,000 cases of malaria were still notified in 1934. Rapid development of the health infrastructure and better socioeconomic conditions improved the malaria situation and reduced the number of cases in 1946. Malaria was completely eradicated in Armenia in 1963, and the malaria-free situation retained till 1994. During that period, comprehensive activities were undertaken in the country to prevent and control malaria. Since 1990, following the collapse of the Soviet Union, the situation became critical in many newly independent states. Economic crisis, human migration, worsening levels of health services, and the lack of necessary medicines, equipment, and insecticides significantly affected the malaria epidemiological situation in the country. Malaria cases started to penetrate into Armenia from neighboring countries. In 1994, a hundred ninety six military men contacted malaria in Karabakh, which was unfavorable in terms of malaria, as well on as the border with Iran and along the Araks river. The first cases recorded in Armenia were imported, afterwards they led to the incidence of indigenous cases, given the fact that all the prerequisites for malaria mosquito breeding and development were encountered in 17 regions and 3 towns of the country. In 1995, there were 502 imported cases and in 1996 the situation changed: out of 347 registered cases, 149 were indigenous. The Ministry of Health undertook a range of preventive measures. In 1997 versus 1996, the total number of malaria cases increased 2.3-fold: 841 registered cases of which 567 were indigenous (a 3.8-fold increase). The overwhelming majority of cases were recorded in the Ararat and Armavir marzes. In 1998, there were a total of 1156 cases, of them 542 being locally contacted. The situation became stable thanks to joint efforts of WHO, IFRX, the Armenian Red Cross Society, UNICEF, the Ministry of Health of Armenia and its Government. Under Minister's Decree No. 292 of May 17, 1999, a malaria project implementation office was established in the Masis Sanitary and Epidemiological Surveillance Center of Hygienic and Antiepidemic Surveillance to improve progress of the malaria control programme in Armenia. WHO allocated some 7,700 USD for 5-month maintenance and work of the office. Thus, analyzing the malaria cases registered in 1999 and 1998 indicates a 1.9-fold decrease (616/77). The setting up the malaria programme field office under the Minister's decree was instrumental in planning and implementing activities in situ. In 1999, four cases of tropical malaria were recorded in Armenia. The patients were Armenian pilots who contacted malaria during duty travels: 1 in Sudan and 3 in Congo. The list of pilots making flying to endemic countries was submitted to the Republican Center to implement preventive measures in the future. In Armenia malaria surveillance has been improved to ensure timely detection of all suspected cases and to carry out malaria control activities. In this regard, a seminar was held for 21 entomologists and 12 parasitologists. UNICEF and WHO Armenian offices provided a substantial support to organize seminars. To facilitate the seminars, the manual "Malaria parasitology and entomology" was published and distributed among their participants. On April 19, 1999, the session of the Ministry's Executive Board (Collegium) gave recommendations to reinforce malaria control activities in the country. Decrees No. 256 of May 31, 1999, No. 47 of May 29, 1999, and No. 245 of April 30, 1999, "On malaria and preventive and control activities" were issued by the Ministry of Health, the Ministry of Defense, and the Ministry of Internal Affairs and National Security to serve as a guideline for planning and implementing activities. The Ministry of Agriculture undertook to clean the collective irrigation (drainage) system covering 102 and 77 km in the Ararat and Armavir marzes, the Ministry of Health provided a list of endemic foci where cleaning was a priority. Taking into account the importance of the people's participation in ensuring effective prevention and control, emphasis was laid on health education activities: publication of leaflets, as well as articles in local newspapers, radio broadcasts and TV shows. Throughout the season, the early detection of malaria cases, timely hospitalization (in no later than 1-3 days) for at least 5 days and subsequent treatment under direct supervision of a physician were successfully carried out due to home-to-home visits. Entomological studies conducted in the malaria foci show an increase in the presence and density of a malaria vector in the buildings. As far as treatment is concerned, the overall surface of stagnant waters comprised 2642 ha in 1999 (2733 ha in 1998), including 1285 ha of anophelogenic stagnant waters (2276 ha in 1998). The biggest stagnant water surfaces were in the Ararat and Armavir marzes--2209 ha, where the majority of malaria cases were recorded. A total of 1,283,111 and 559,213 sq. m. of constructions were treated in 1999 and 1998, respectively, out them there were 1,259,637 sq. m. in 5 endemic regions. Stagnant water surfaces were treated with bacticulicides on 250.7 and 743.8 (almost 3 times more) in 1998 and 1999, respectively. In 1999, 740 ha of surface were biologically treated using Gambusia compared to 900 ha treated in 1998. There is no highly qualified diagnostic specialists in many regions of the country, which necessitates the holding of further seminars involving relevant specialists, in all malaria regions. There is a tendency of geographical spread of malaria: malaria cases occur in new regions and dwellings. A country-wide action plan was drafted for 2000, mainly focusing on staff training. With WHO assistance, a seminar was held for 324 specialists from endemic regions. During the first quarter of 2000, 13 cases of tertian malaria were recorded as compared 59 cases during the same period of last year. All these patients contacted malaria in the previous season and demonstrated long incubation periods. Thus, the malaria control plan recommended by WHO and the rational and targeted use of its assistance has shown a 2-fold decrease in the incidence of malaria.
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PMID:[Armenia: implementation of national program of malaria control]. 1154 7

The development of primary health care in Jamaica is explored, tracing its early roots to the abolition of the slave trade, the collapse of estate-based services after emancipation and the subsequent establishment of the Island Medical Services in 1875. Most development in the health sector occurred after World War I in response to the high infectious disease mortality rates. The Rockefeller Foundation was asked to assist with the control of hookworm, tuberculosis, malaria and yaws. Its recommendations led to the growth of public health programmes (e.g. environmental health, public health nursing, community midwifery) alongside community-based curative services run by hospitals. The most significant period of development occurred in the 1970s when the various vertical programmes were integrated into the current primary care system. Jamaica was integral in the development of the World Health Organization's Alma Ata Declaration on Primary Health Care, tabling the "Jamaican Perspective on Primary Health Care" which set out its goal that all citizens should be within 10 miles walking distance of a primary health care facility. At the close of the twentieth century, the health reform process led to the development of regional health authorities aimed at integrating the management of primary and secondary care under four Regional Boards of Health. This has led to a change in the role of the central Ministry of Health to one of policy-making, health promotion, setting standards, monitoring and evaluation of the quality of health care.
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PMID:The development of primary health care in Jamaica. 1182 20

Neurological malaria, characterized by significant cerebral involvement, is the most worrisome aspect of Plasmodium falciparum malaria, with a mortality rate of 10-30%. Neurological malaria is generally limited to immunodepressed subjects. Children aged 4 months to 4 years and foreigners who have neglected their chemical prophylaxis are at risk. In weakly endemic areas, native adults who have not built up immunity may also be at risk. 1844 children hospitalized for malaria were studied in 1995 for clinical indicators of gravity. The risk of death was evaluated for each of 10 criteria suggested by the World Health Organization and 5 simple additional parameters. An initial coma, cardiovascular collapse, and repeated convulsions were major factors in mortality. Acute anemia, acidosis, and elevated parasite levels did not worsen the prognosis, but severe hypoglycemia, severe respiratory distress, and jaundice were associated with poor outcomes. The majority of children who died suffered respiratory distress on admission to the hospital, which often complicated the diagnosis of malaria. Nearly all died within 24 hours of admission. Knowledge of the factors associated with mortality should facilitate referral of patients who need higher levels of care.
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PMID:[Criteria of gravity of neurological malaria in children]. 1232 46

Malaria is often a major health problem in war-torn countries in the tropics owing to the collapse of health services and the vulnerability of displaced populations to epidemics. Insecticide-treated nets (ITN) represent one of the few options for obtaining protection against malaria in unstable settings deficient in health infrastructure. Social marketing of subsidized ITN by a consortium of non-governmental organizations began in Afghanistan in 1993 and has continued every year since then despite regular political turmoil. Almost 350,000 nets have been sold and approximately 1.2 million people protected. In 2000 we examined the determinants of ITN purchasing among households in Nangarhar province, eastern Afghanistan, as part of an effort to increase ITN uptake. The survey was conducted using a structured questionnaire to collect data on socio-economic characteristics and malaria beliefs and practices among more than 400 net-owning and non-net-owning households. A composite socio-economic index was created using principal components analysis, and survey households were divided into socio-economic quartiles. ITN were 4.5 times more likely to be purchased by families from the richest quartile and 2.3 times more likely to be purchased from the upper-middle quartile than from the two lower quartiles. Even so, a significant minority from the lower quartiles did prioritize and buy ITN. In conflict affected countries where livelihoods are compromised, it is necessary to target subsidies at the most impoverished to make ITN affordable and to improve overall coverage.
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PMID:Socio-economic factors associated with the purchasing of insecticide-treated nets in Afghanistan and their implications for social marketing. 1464 38


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