Interleukin-18 levels in induced sputum are reduced in asthmatic and normal smokers.

BACKGROUND: IL-18 is a cytokine which is known to have an important role in the development of a Th1 lymphocyte response. As such, it may have a regulatory role in asthma by modifying Th2 lymphocyte responses. Cigarette smoking may amplify the airway inflammation associated with asthma. OBJECTIVE: This study investigated if IL-18 could be detected in induced sputum from asthmatics and normal subjects and if smoking altered IL-18 levels. METHODS: Induced sputum was obtained from asthmatic (31 smokers, 35 non-smokers) and normal (20 smokers, 20 non-smokers) subjects. All smokers had a smoking history of > or =15 pack years. IL-18 levels in sputum supernatant were measured by ELISA. IL-18 mRNA expression and cellular localization were assessed by quantitative PCR and immunocytochemistry, respectively. RESULTS: Smoking was associated with a significant reduction in IL-18 levels (median (interquartile range) - smokers 20 (0-102) pg/mL vs. non-smokers 358 (50-876) pg/mL, P<0.001). This was more pronounced in asthmatics (smokers, 47 (40-64) pg/mL vs. non-smokers, 530 (30-1484) pg/mL; P<0.001) than in normal subjects (smokers, 25 (0-78) pg/mL vs. non-smokers, 247 (50-656) pg/mL; P<0.01). Within each of the smoking and non-smoking groups there was no significant difference in IL-18 levels between asthmatic and normal subjects. There was no correlation between sputum IL-18 levels and any specific cell type in the sputum samples nor serum IgE levels. IL-18 mRNA expression was reduced in asthmatic smokers compared with non-smokers. IL-18 production was localized to sputum macrophages by immunocytochemistry. CONCLUSIONS: IL-18 is detectable in induced sputum samples from both asthmatic and normal subjects. Cigarette smoking significantly reduces sputum IL-18 levels. This effect is more pronounced in asthmatics than in normal subjects.

Modulation of macrophage cytokine production by ES-62, a secreted product of the filarial nematode Acanthocheilonema viteae.

Parasite survival and host health may depend on the ability of the parasite to modulate the host immune response by the release of immunomodulatory molecules. Excretory-secretory (ES)-62, one such well-defined molecule, is a major secreted protein of the rodent filarial nematode Acanthocheilonema viteae, and has homologues in human filarial nematodes. Previously we have shown that ES-62 is exclusively associated with a Th2 Ab response in mice. Here we provide a rationale for this polarized immune response by showing that the parasite molecule suppresses the IFN-gamma/LPS-induced production, by macrophages, of bioactive IL-12 (p70), a key cytokine in the development of Th1 responses. This suppression of the induction of a component of the host immune response extends to the production of the proinflammatory cytokines IL-6 and TNF-alpha, but not NO. The molecular mechanism underlying these findings awaits elucidation but, intriguingly, the initial response of macrophages to ES-62 is to demonstrate a low and transient release of these cytokines before becoming refractory to further release induced by IFN-gamma/LPS. The relevance of our observations is underscored by the finding that macrophages recovered from mice exposed to "physiological" levels of ES-62 by the novel approach of continuous release from implanted osmotic pumps in vivo were similarly refractory to release of IL-12, TNF-alpha, IL-6, but not NO, ex vivo. Therefore, our results suggest that exposure to ES-62 renders macrophages subsequently unable to produce Th1/proinflammatory cytokines. This likely contributes to the generation of immune responses with an anti-inflammatory Th2 phenotype, a well-documented feature of filarial nematode infection.

A novel pathway regulating lipopolysaccharide-induced shock by ST2/T1 via inhibition of Toll-like receptor 4 expression.

ST2/ST2L, a member of the IL-1R gene family, is expressed by fibroblasts, mast cells, and Th2, but not Th1, cells. It exists in both membrane-bound (ST2L) and soluble forms (ST2). Although ST2L has immunoregulatory properties, its ligand, cellular targets, and mode of action remain unclear. Using a soluble ST2-human IgG fusion protein, we demonstrated that ST2 bound to primary bone marrow-derived macrophages (BMM) and that this binding was enhanced by treatment with LPS. The sST2 treatment of BMMs inhibited production of the LPS-induced proinflammatory cytokines IL-6, IL-12, and TNF-alpha but did not alter IL-10 or NO production. Treatment of BMMs with sST2 down-regulated expression of Toll-like receptors-4 and -1 but induced nuclear translocation of NF-kappaB. Administration of sST2 in vivo after LPS challenge significantly reduced LPS-mediated mortality and serum levels of IL-6, IL-12, and TNF-alpha. Conversely, blockade of endogenous ST2 through administration of anti-ST2 Ab exacerbated the toxic effects of LPS. Thus, ST2 has anti-inflammatory properties that act directly on macrophages. We demonstrate here a novel regulatory pathway for LPS-induced shock via the ST2-Toll-like receptor 4 route. This may be of considerable therapeutic potential for reducing the severity and pathology of inflammatory diseases.

Regulation of ornithine decarboxylase activity and polyamine transport by agmatine in rat pulmonary artery endothelial cells.

Agmatine, a product of arginine decarboxylation in mammalian cells, is believed to govern cell polyamines by inducing antizyme, which in turn suppresses ornithine decarboxylase (ODC) activity and polyamine uptake. However, since agmatine is structurally similar to the polyamines, it is possible that it exerts antizyme-independent actions on polyamine regulatory pathways. The present study determined whether agmatine inhibited ODC activity and polyamine transport in rat pulmonary artery endothelial cells (PAECs) by an antizyme-dependent mechanism. Agmatine caused time-dependent reductions in ODC activity, which occurred before increases in antizyme. Interventions that suppressed proteasome function caused large increases in ODC activity but failed to attenuate inhibitory effects of agmatine. When agmatine was present in the culture medium, 14C-polyamine uptake was competitively inhibited as evidenced by substantial elevations in K(m) values. If PAECs were incubated with agmatine for periods sufficient to increase antizyme, there were modest decreases in V(max) for putrescine and spermidine but not for spermine. These effects of agmatine on polyamine transport were insensitive to protein synthesis inhibition. Collectively, our findings show that agmatine decreases ODC activity and polyamine transport in PAECs, but a causal role for antizyme in these actions of agmatine is difficult to establish. Nevertheless, these observations are consistent with a model in which PAECs express both antizyme-1 and -2, but only the latter contributes to agmatine-mediated suppression of ODC activity.

Decreased regional brain metabolism after ect.

OBJECTIVE: The antidepressant action of ECT may be related to its anticonvulsant properties. Positron emission tomography (PET) studies of regional cerebral metabolic rate for glucose were used to test this hypothesis. METHOD: Ten patients with major depression were studied with PET before and approximately 5 days after a course of bilateral ECT. Statistical parametric mapping was used to identify regions of decreased cerebral glucose metabolism. RESULTS: Widespread regions of decreased regional cerebral glucose metabolism were identified after ECT, especially in the frontal and parietal cortex, anterior and posterior cingulate gyrus, and left temporal cortex. A region-of-interest analysis similarly indicated post-ECT reductions in regional cerebral glucose metabolism. CONCLUSIONS: ECT reduces neuronal activity in selected cortical regions, a potential anticonvulsant and antidepressant effect.

Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission I. Description of study site, general methodology, and study population.

A large-scale longitudinal cohort project was initiated in western Kenya in June 1992. The primary purpose of the project was to study Plasmodium falciparum malaria in a highly endemic area using a comprehensive and multidisciplinary approach, which included epidemiology, entomology, and immunology. Between June 1992 and July 1994, pregnant women living in 15 rural villages were identified during a monthly census and 1,164 were enrolled. The women were followed-up throughout their pregnancy and they, along with their newborn infants and direct siblings of the infants' less than 15 years of age, were monitored over time. As of May 1995, 1,017 infants had been born to these women. This paper presents the design and general methodology used in this study and describes the initial experience with intense monitoring of a large population over a prolonged period.

Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children.

A large-scale longitudinal cohort project was initiated in western Kenya in June 1992. Between June 1992 and July 1994, 1,848 children less than 15 years of age were monitored prospectively for a mean of 236 days. During this period, 12,035 blood smears were examined for malaria and only 34% were found to be negative. Parasite prevalence (all species) decreased with age (from a high of 83% among children 1-4 years old to 60% among children 10-14 years old). Even more dramatic decreases were noted in the prevalence of high density falciparum infection (from 37% among children 12-23 months old to < 1% among 10-14-year-old children) and in clinical malaria (20% to 0.3% in the same age groups). Children < 1 year of age accounted for 55% of all cases of anemia detected. Anemia was consistently associated with high density infection in children < 10 years of age (20% to 210% increased risk relative to aparasitemic children). These results demonstrate the relationship between high-density malaria infection and two clinical manifestations of malarial illness.

Longitudinal evaluation of severely anemic children in Kenya: the effect of transfusion on mortality and hematologic recovery.

OBJECTIVE: To determine the effect of transfusion on hematologic recovery and mortality among severely anemic children during and after hospitalization in rural Kenya. DESIGN: Prospective cohort. METHODS: We collected clinical and laboratory information on all severely anemic children (hemoglobin < 5.0 g/dl) and a 33% sample of children with hemoglobin < or = 5.0 g/dl who were admitted to the pediatric ward of a rural Kenyan hospital during a 6 month study period. Children were followed during hospitalization and at 4 and 8 weeks after admission. RESULTS: Overall, 303 (25%) of the 1223 hospitalized children had hemoglobin < 5.0 g/dl, 30% of whom died during the study period. Severely anemic children who were transfused had a higher mean hemoglobin level at discharge (9.0 g/dl) than non-transfused children (5.8 g/dl, P < 0.001) and maintained a higher mean hemoglobin during the 8-week follow-up period. However, the presence of malaria parasitemia on follow-up negated the benefit of transfusion on hematologic recovery at both 4- and 8-week visits (longitudinal linear model, least square means, P > 0.05). Transfusion was associated with improved survival among children with respiratory distress who received transfusions within the first 2 days of hospitalization. CONCLUSIONS: The use of transfusion can be improved by targeting use of blood to severely anemic children with cardiorespiratory compromise, improving immediate availability of blood, and treating severely anemic children with effective antimalarial therapy.

PIP: The effect of blood transfusion on hematologic recovery and mortality both during and after hospitalization was investigated in a survey of children admitted to Siaya District Hospital (Kenya) in a 6-month period in 1991 with hemoglobin under 5.0 g/dl (n = 303) or 5.0 g/dl and above (n = 303). Children with hemoglobin under 5.0 g/dl (severe anemia) were younger and more likely to have malaria parasitemia and respiratory compromise than controls. 88 severely anemic children (30%) died during the study period. Severely anemic children who were transfused had a higher mean hemoglobin level at discharge (9.0 g/dl) than nontransfused children (5.8 g/dl) and maintained a higher mean hemoglobin in the 8-week post-discharge follow-up period. 15% of transfused and 17% of nontransfused children died after hospital discharge. Transfusion was associated with significantly improved survival among children with respiratory distress who were transfused within 2 days of hospital admission. However, the presence of malaria or parasitemia at follow-up negated the benefit of transfusion on hematologic recovery. These findings suggest that the effectiveness of transfusion can be enhanced by targeting severely anemic children with cardiorespiratory compromise, improving immediate access to blood, and effective antimalarial therapy. In addition, more information is needed on the causes of death among anemic children and the prevention of severe anemia.

Malaria: an emerging and re-emerging global plague.

PIP: Worldwide, malaria is the most prevalent infectious disease affecting humans. Malaria parasites presently infect more than 500 million people annually, killing up to 2 million and causing at least 100 million cases of acute illness. At the macroepidemiologic level, malaria is therefore an established, endemic public health plague for about one-third of the world's population. At the microepidemiologic level, malaria is a highly dynamic infection and disease. Although some countries have effectively managed the threat of malaria, there has been a dramatic, worldwide increase in malaria-related morbidity and mortality over the past 2 decades. In many parts of the globe, malaria is both a major threat to public health and a major obstacle to development given its ability to create high public health costs, lost productivity, and impaired individual growth. Plasmodium falciparum infections, regional differences and changes in malaria epidemiology, drug resistance, changing malaria control strategies, and implementing malaria control in Africa are discussed.^ieng

Malaria surveillance--United States, 1993.

PROBLEM/CONDITION: Malaria is caused by infection with one of four species of Plasmodium (P. falciparum, P. vivax, P. ovale, and P. malariae), which are transmitted by the bite of an infective female Anopheles sp. mosquito. Most malaria cases in the United States occur among persons who have traveled to areas (i.e., other countries) in which disease transmission is ongoing. However, cases are transmitted occasionally through exposure to infected blood products, by congenital transmission, or by local mosquito-borne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations. REPORTING PERIOD COVERED: Cases with onset of illness during 1993. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood smear are reported to local and/or state health departments by health-care providers and/or laboratories. Case investigations are conducted by local and/or state health departments, and the reports are transmitted to CDC. RESULTS: CDC received reports of 1,275 cases of malaria in persons in the United States and its territories who had onset of symptoms during 1993; this number represented a 40% increase over the 910 malaria cases reported for 1992. P. vivax, P. falciparum, P. ovale, and P. malariae were identified in 52%, 36%, 4%, and 3% of cases, respectively. The species was not determined in the remaining 5% of cases. The 278 malaria cases in U.S. military personnel represented the largest number of such cases since 1972; 234 of these cases were diagnosed in persons returning from deployment in Somalia during Operation Restore Hope. In New York City, the number of reported cases increased from one in 1992 to 130 in 1993. The number of malaria cases acquired in Africa by U.S. civilians increased by 45% from 1992; of these, 34% had been acquired in Nigeria. The 45% increase primarily reflected cases reported by New York City. Of U.S. civilians who acquired malaria during travel, 75% had not used a chemoprophylactic regimen recommended by CDC for the area in which they had traveled. Eleven cases of malaria had been acquired in the United States: of these cases, five were congenital; three were induced; and three were cryptic, including two cases that were probably locally acquired mosquito-borne infections. Eight deaths were associated with malarial infection. INTERPRETATION: The increase in the reported number of malaria cases was attributed to a) the number of infections acquired during military deployment in Somalia and b) complete reporting for the first time of cases from New York City. ACTIONS TAKEN: Investigations were conducted to collect detailed information concerning the eight fatal cases and the 11 cases acquired in the United States. Malaria prevention guidelines were updated and disseminated to health-care providers. Persons who have a fever or influenza-like illness after returning from a malarious area should seek medical care, regardless of whether they took antimalarial chemoprophylaxis during their stay. The medical evaluation should include a blood smear examination for malaria. Malaria can be fatal if not diagnosed and treated rapidly. Recommendations concerning prevention and treatment of malaria can be obtained from CDC.

Evaluation of an algorithm for integrated management of childhood illness in an area of Kenya with high malaria transmission.

In 1993, the World Health Organization completed the development of a draft algorithm for the integrated management of childhood illness (IMCI), which deals with acute respiratory infections, diarrhoea, malaria, measles, ear infections, malnutrition, and immunization status. The present study compares the performance of a minimally trained health worker to make a correct diagnosis using the draft IMCI algorithm with that of a fully trained paediatrician who had laboratory and radiological support. During the 14-month study period, 1795 children aged between 2 months and 5 years were enrolled from the outpatient paediatric clinic of Siaya District Hospital in western Kenya; 48% were female and the median age was 13 months. Fever, cough and diarrhoea were the most common chief complaints presented by 907 (51%), 395 (22%), and 199 (11%) of the children, respectively; 86% of the chief complaints were directly addressed by the IMCI algorithm. A total of 1210 children (67%) had Plasmodium falciparum infection and 1432 (80%) met the WHO definition for anaemia (haemoglobin < 11 g/dl). The sensitivities and specificities for classification of illness by the health worker using the IMCI algorithm compared to diagnosis by the physician were: pneumonia (97% sensitivity, 49% specificity); dehydration in children with diarrhoea (51%, 98%); malaria (100%, 0%); ear problem (98%, 2%); nutritional status (96%, 66%); and need for referral (42%, 94%). Detection of fever by laying a hand on the forehead was both sensitive and specific (91%, 77%). There was substantial clinical overlap between pneumonia and malaria (n = 895), and between malaria and malnutrition (n = 811). Based on the initial analysis of these data, some changes were made in the IMCI algorithm. This study provides important technical validation of the IMCI algorithm, but the performance of health workers should be monitored during the early part of their IMCI training.

PIP: The World Health Organization (WHO) in 1993 developed the integrated management of childhood illness (IMCI) draft algorithm which offers guidelines upon the diagnosis and treatment of acute respiratory infections, diarrhea, malaria, measles, ear infections, and malnutrition, as well as immunization status. During a 14-month study period, 1795 children aged 2 months to 5 years were enrolled in the study from the outpatient pediatric clinic of Siaya District Hospital in western Kenya, of whom 52% were male and the median age was 13 months. 51% of the children complained of having fever, 22% of having a cough, and 11% of having diarrhea. 86% of the main complaints were directly addressed by the IMCI algorithm. 1210 children had Plasmodium falciparum infection and 1432 met the WHO definition for anemia. The sensitivities and specificities for classification of illness by a minimally trained health worker using the IMCI algorithm compared to diagnosis by the physician were: pneumonia, 97% sensitivity and 49% specificity; dehydration in children with diarrhea, 51% and 98%, respectively; malaria, 100% and 0%; ear problem, 98% and 2%; nutritional status, 96% and 66%; and need for referral, 42% and 94%. Detection of fever by placing a hand upon the forehead was 91% sensitive and 77% specific. Considerable clinical overlap was observed between pneumonia and malaria, and between malaria and malnutrition. Study findings led to some changes in the IMCI algorithm.

Clinical signs for the recognition of children with moderate or severe anaemia in western Kenya.

Optimal treatment of Plasmodium falciparum-related paediatric anaemia can result in improved haematological recovery and survival. Clinical predictors are needed to identify children with anaemia in settings where laboratory measurements are not available. The use of conjunctival (eyelid), palmar, nailbed, and tongue pallor to detect children with moderate anaemia (haemoglobin, 5.0-7.9 g/dl) or severe anaemia (haemoglobin, < 5.0 g/dl) was evaluated among children seen at an outpatient and inpatient setting in a hospital in western Kenya. Severe nailbed or severe palmar pallor had the highest sensitivity (62% and 60%, resp.), compared with severe conjunctival pallor (sensitivity = 31%), to detect children with severe anaemia in the outpatient setting. Children with moderate anaemia were best identified by the presence of nailbed or palmar pallor (sensitivity = 90% for both signs), compared with conjunctival pallor (sensitivity = 81%). Clinical signs of respiratory distress, in addition to the presence of severe pallor, did not increase the recognition of children requiring hospitalization for severe anaemia. Among inpatients, the sensitivity of severe nailbed pallor (59%) was highest for detecting children with severe anaemia, although the sensitivity of severe conjunctival pallor and severe palmar pallor was the same (53% for both signs). Presence of conjunctival pallor (sensitivity = 74%) was similar in sensitivity to both nailbed and palmar pallor (70% for both signs) among children with moderate anaemia. The sensitivity of tongue pallor was low among all children evaluated. Low haemoglobin levels were significantly associated with the likelihood of being smear-positive for P. falciparum. This study demonstrates that clinical criteria can be used to identify children with moderate and severe anaemia, thus enabling implementation of treatment algorithms. Children aged < 36 months who live in an area with P. falciparum malaria should receive treatment with an effective antimalarial drug if they have pallor.

PIP: The ability of pallor of the conjunctiva, palms, nailbed, and tongue to identify children with Plasmodium falciparum-related anemia in developing country settings, where laboratory measurements are not available, was investigated in children attending Siaya District Hospital in western Kenya. Enrolled were all children 2 months to 5 years of age admitted to the hospital's inpatient unit in 1993-94 (n = 1048), and every fifth child presenting to the outpatient clinic (n = 1666). Severe nailbed or severe palmar pallor had the highest sensitivities (62% and 60%, respectively) in the detection of severe anemia in outpatients, while those with moderate anemia were best identified by nailbed or palmar pallor (90% sensitivity for both signs). The addition of clinical signs of respiratory distress to pallor did not increase the identification of children requiring hospitalization for severe anemia. Among inpatients, severe nailbed, conjunctival, and palmar pallor had sensitivities of 59%, 53%, and 53%, respectively, for detecting severe anemia. In the detection of moderate anemia, the sensitivities were 74%, 70%, and 70%, respectively, for conjunctival, nailbed, and palmar pallor. Tongue pallor had a low sensitivity among all children examined. Low hemoglobin levels were significantly associated with P. falciparum infection. It is recommended that all children under 36 months of age, in areas with P. falciparum malaria, should receive antimalarial treatment if they present with pallor.

Childhood mortality during and after hospitalization in western Kenya: effect of malaria treatment regimens.

Plasmodium falciparum infection is an important cause of the high childhood mortality rates in sub-Saharan Africa. Increasingly, the contribution of P. falciparum-associated severe anemia to pediatric mortality is being recognized while the impact of chloroquine resistance on mortality has not been evaluated. To address the issues of pediatric mortality, causes of death among hospitalized children less than five years of age in western Kenya were identified using standardized clinical examinations and laboratory evaluations. Follow-up examinations were conducted to determine the child's clinical status posthospitalization. Of the 1,223 children admitted to Siaya District Hospital from March to September 1991, 293 (24%) were severely anemic (hemoglobin level < 5.0 g/dL). There were 265 (22%) deaths; 121 (10%) occurred in-hospital and 144 (13%) occurred out-of-hospital within eight weeks after admission; 32% of all deaths were associated with malaria. Treatment for malaria with chloroquine was associated with a 33% case fatality rate compared with 11% for children treated with more effective regimens (pyrimethamine/sulfa, quinine, or trimethoprim/sulfamethoxazole for five days). The risk of dying was associated with younger age (P < 0.0001) and severe anemia (relative risk [RR] = 1.52, 95% confidence interval [CI] = 1.22, 1.90), and was decreased by treatment with an effective antimalarial drug (RR = 0.33, 95% CI = 0.19, 0.65). Effective drug therapy for P. falciparum with regimens that are parasitocidal in areas with a high prevalence of severe anemia and chloroquine resistance can significantly improve the survival of children in Africa.

PIP: Plasmodium falciparum infection is an important cause of the high childhood mortality rates in sub-Saharan Africa. Causes of death among hospitalized children less than age 5 years in western Kenya were identified using standardized clinical examinations and laboratory evaluations. Follow-up examinations were then conducted to determine the child's clinical status posthospitalization. 293 of the 1223 children admitted to Siaya District Hospital during March-September 1991 were severely anemic. 265 children died; 32% of the deaths were associated with malaria. 121 of the deaths occurred in-hospital and 144 out-of-hospital within 8 weeks after admission. The treatment of malaria with chloroquine was associated with a 33% case fatality rate compared with 11% for children treated with more effective regimens of pyrimethamine/sulfa, quinine, or trimethoprim/sulfamethoxazole for 5 days. The risk of dying was associated with younger age and severe anemia, and was decreased by treatment with an effective antimalarial drug.

Etiologies of shoulder pain in cervical spinal cord injury.

A protocol including physical examination, plain radiography, and shoulder arthrography was designed to study prospectively the causes of shoulder pain in patients with cervical spinal cord injury. Twenty-four patients (30 shoulders) were studied and subdivided into acute and chronic groups. The causes of shoulder pain in the acute group of 11 patients (15 shoulders) included capsular contracture or capsulitis or both in 6 shoulders; rotator cuff tears in 4; anterior instability in 2; and rotator cuff impingement, osteoarthritis with osteonecrosis, and osteoarthritis in 1 each. Of 13 patients (15 shoulders) assigned to the chronic group, the diagnoses included anterior instability in 5 shoulders; multidirectional instability in 3; capsular contracture or capsulitis or both in 3; and Charcot arthropathy, rotator cuff tear, rotator cuff impingement, and scapular pain in 1 each. To prevent and treat shoulder pain, therapeutic protocols for these patients must be individualized after a correct diagnosis is made.

Developing effective strategies for malaria prevention programs for pregnant African women.

The control of malaria in pregnant African women, one of several child survival strategies applied through antenatal care, has been particularly challenging. Prevention and control recommendations for typical areas of high Plasmodium falciparum transmission have promoted the use of antimalarial chemoprophylaxis to prevent placental infection. Persistently low program coverage coupled with diminishing intervention effectiveness have forced a re-evaluation of the relative importance of malaria in pregnancy. The Mangochi Malaria Research Project (MMRP), a prospective evaluation of malaria prevention in pregnant women in rural Malawi conducted during 1987-1990, contributed to establishing new criteria for policy and program development for malaria prevention in pregnancy. The principle findings of the MMRP include: 1) populations at risk of the adverse consequences of malaria in pregnancy include women with low parity, women infected with human immunodeficiency virus, pregnancy during the high malaria transmission season, and the use of a malaria drug that is suboptimally efficacious; 2) the estimated maximum benefits of an antimalarial intervention that clears placental and umbilical cord parasitemia are a 5-12% reduction of low birth weight (LBW), an approximately 35% reduction in the risk of LBW for risks that are actually preventable once a woman has become pregnant (e.g., risks such as infectious disease or poor nutrition during gestation), and a 3-5% reduction in the rate of infant mortality; 3) the intervention must be capable of rendering the woman malaria parasite free, including clearance of parasites from the placental vascular space and umbilical cord blood; 4) other diseases adversely affect pregnancy outcome and, while the control of malaria in pregnancy may not warrant independent programming, if coupled with prevention programs to provide a range of antenatal services, the incremental costs of malaria control may prove to be highly cost-effective; and 5) the choice of a regimen must balance intervention efficacy with safety, availability, affordability, and simplicity of delivery, and several antimalarials may meet these criteria. The Malawi Ministry of Health has modified its malaria prevention in pregnancy recommendations and now faces the challenge of effective programming to improve child survival.

PIP: During 1987-90, a prospective evaluation of malaria prevention in pregnant women in rural Malawi, the Mangochi Malaria Research Project, was conducted. It aimed to address systematically the evolving obstacles to effective program strategies. The findings contribute to the establishment of new criteria for decision-making in policy and program development for malaria prevention and control in pregnancy. The project resulted in five key lessons learned. Populations at risk of the adverse effects of malaria during pregnancy are low-parity women, HIV-infected women, women pregnant during the high malaria transmission season, and pregnant women using a less effective malaria drug. The estimated maximum benefits of an antimalarial intervention include a 5-12% reduction in low birth weight (LBW), an approximate 35% reduction in the risk of LBW for risks that are preventable once a woman has conceived (i.e., infectious disease or poor nutrition during pregnancy), and a 3-5% reduction in infant mortality. The antimalarial intervention must be able to make the pregnant women malaria-parasite free and to effect clearance of parasites from the placental vascular space and umbilical cord blood. Since other diseases also adversely affect pregnancy outcome, the control of malaria should be integrated with prevention programs to provide a range of prenatal services. When choosing a regimen, the health provider must balance the regimen's efficacy with safety, availability, affordability, and ease of delivery. Several antimalarial regimens appear to meet these criteria. Based on the findings of the project, the Malawi Ministry of Health has changed its recommendations for malaria prevention in pregnancy.

Malaria surveillance--United States, 1992.

PROBLEM/CONDITION: Malaria is caused by one of four species of Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae) and is transmitted by the bite of an infective female Anopheles sp. mosquito. Most malaria cases in the United States occur among persons who have traveled to areas that have ongoing transmission. However, cases are transmitted occasionally through exposure to infected blood products, by congenital transmission, or by local mosquito-borne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations. REPORTING PERIOD COVERED: Cases with onset of illness during 1992. DESCRIPTION OF SYSTEM: Malaria cases were identified at the local level (i.e., by healthcare providers or through laboratory-based surveillance). All suspected cases were confirmed by slide diagnosis and then reported to the respective state health department and to CDC. RESULTS: CDC received reports of 910 cases of malaria that had onset of symptoms during 1992 among persons in the United States and its territories. In comparison, 1,046 cases were reported for 1991, representing a decrease of 13% in 1992. P. vivax, P. falciparum, P. malariae, and P. ovale were identified in 51%, 33%, 4%, and 3% of cases, respectively. The species was not identified in the remaining 9% of cases. The number of reported malaria cases that had been acquired in Africa by U.S. civilians decreased 38%, primarily because the number of P. falciparum cases declined. Of U.S. civilians whose illnesses were diagnosed as malaria, 81% had not taken a chemoprophylactic regimen recommended by CDC. Seven patients had acquired their infections in the United States. Seven deaths were attributed to malaria. INTERPRETATION: The decrease in the number of P. falciparum cases in U.S. civilians could have resulted from a change in travel patterns, reporting errors, or increased use of more effective chemoprophylaxis regimens. ACTIONS TAKEN: Additional information was obtained concerning the seven fatal cases and the seven cases acquired in the United States. Malaria prevention guidelines were updated and disseminated to health-care providers. Persons traveling to a malaria-endemic area should take the recommended chemoprophylaxis regimen and use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently develops a fever or influenza-like symptoms should seek medical care, which should include a blood smear for malaria. The disease can be fatal if not diagnosed and treated at an early stage of infection. Recommendations concerning prevention and treatment of malaria can be obtained from CDC.

Mosquito-transmitted malaria in New York City, 1993.

In August, 1993, 3 cases of Plasmodium falciparum malaria in people without recent travel histories or bloodborne exposure were reported in New York City. An epidemiological investigation confirmed the absence of risk factors for acquisition of malaria in two cases. The third case could not be definitively classified as locally acquired malaria because the patient had travelled to Thailand two years before malaria was diagnosed. The 3 individuals lived in separate houses in the same neighbourhood of Queens, New York and had onset of illness within a day of each other. The investigation consisted of patient interviews, active case finding, reviewing recent New York flight and shipping arrivals, and an entomological survey for anopheline mosquitoes and breeding sites. No other cases were identified. The 3 patients lived several miles from air and sea ports and prevailing winds would have carried any mosquitoes at those sites away from the patient's homes. By the time of the environmental investigation (September, 1993), the area was dry and neither adult nor larval anophelines were found. However, weather conditions at the probable time of infection (July, 1993) were very different. Malaria was probably transmitted to these 2 patients by local anopheline mosquitoes that had fed on infected human hosts. Mosquito-control measures were not implemented because there was no evidence of ongoing transmission. The occurrence of mosquito-transmitted malaria in New York City demonstrates the potential for reintroduction of malaria transmission into areas that are no longer endemic and emphasises the need for continued surveillance and prompt investigations, if cases without risk factors are reported.