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Immune responses to band 3 neoantigens on Plasmodium falciparum-infected erythrocytes in subjects living in an area of intense malaria transmission are associated with low parasite density and high hematocrit value.

During the intracellular development of the human malarial parasite, Plasmodium falciparum, cryptic regions of the erythrocyte band 3 protein are exposed. Antibodies against these band 3-related neoantigens block cytoadherence, and peptides based on amino acid sequences of putative exofacial loops of band 3 protein block the in vitro and in vivo adherence of P. falciparum-infected erythrocytes. At present, it is not known whether reactivity to these antigens is related to exposure to the malaria parasite or is correlated with protective immunity. The reactivities of plasma to peptides containing amino acid sequences of putative exofacial loops 3 and 7 of human band 3 protein were determined for children and adults living in an area of perennial malaria transmission (Liberia) and for donors who had never been exposed to malaria (Denmark). Plasma samples from children and adults living in an area of intense malaria transmission showed a much higher reactivity with the band 3 peptides than did those from nonimmune individuals. High reactivity to the loop 3 peptide (amino acids 546 to 555) was correlated with lower mean parasite density in children in the 5- to 9-year-old age group. The presence of antibodies against loop 3 and 7 peptides was not associated with a low packed erythrocyte volume (hematocrit); in fact, higher-than-average reactivities to both peptides were positively correlated with high hematocrit values, indicating that antibodies which specifically recognize the band 3-related neoantigens are not involved in hemolysis (autoimmunity).

Adolescent↗

Selection of glutamate-rich protein long synthetic peptides for vaccine development: antigenicity and relationship with clinical protection and immunogenicity.

Antibodies against three long synthetic peptides (LSPs) derived from the glutamate-rich protein (GLURP) of Plasmodium falciparum were analyzed in three cohorts from Liberia, Ghana, and Senegal. Two overlapping LSPs, LR67 and LR68, are derived from the relatively conserved N-terminal nonrepeat region (R0), and the third, LR70, is derived from the R2 repeat region. A high prevalence of antibody responses to each LSP was observed in all three areas of endemic infection. Levels of cytophilic immunoglobulin G (IgG) antibodies against both GLURP regions were significantly correlated with protection from clinical P. falciparum malaria. Protected children from the Ghana cohort possessed predominantly IgG1 antibodies against the nonrepeat epitope and IgG3 antibodies against the repeat epitope. T-cell proliferation responses, studied in the cohort from Senegal, revealed that T-helper-cell epitopes were confined to the nonrepeat region. When used as immunogens, the LR67 and LR68 peptides elicited strong IgG responses in outbred mice and LR67 also induced antibodies in mice of different H-2 haplotypes, confirming the presence of T-helper-cell epitopes in these constructs. Mouse antipeptide antisera recognized parasite proteins as determined by immunofluorescence and immunoblotting. This indicates that synthetic peptides derived from relatively conserved epitopes of GLURP might serve as useful immunogens for vaccination against P. falciparum malaria.

Adolescent↗

Early diagnosis of Lassa fever by reverse transcription-PCR.

We developed a method based on a coupled reverse transcription-PCR (RT-PCR) for the detection of Lassa virus using primers specific for regions of the S RNA segment which are well conserved between isolates from Sierra Leone, Liberia, and Nigeria. The specificity of the assay was confirmed by Southern blotting with a chemiluminescent probe. The assay was able to detect 1 to 10 copies of a plasmid or an RNA transcript containing the target sequence. There was complete concordance between RT-PCR and virus culture for the detection of Lassa virus in a set of 29 positive and 32 negative serum samples obtained on admission to the hospital from patients suspected of having Lassa fever in Sierra Leone. Specificity was confirmed by the failure of amplification of specific products from serum samples collected from 129 healthy blood donors in Sierra Leone or from tissue culture supernatants from cells infected with related arenaviruses (Mopeia, lymphocytic choriomeningitis, Tacaribe, and Pichinde viruses). Sequential serum samples from 29 hospitalized patients confirmed to have Lassa fever were tested by RT-PCR and for Lassa virus-specific antibodies by indirect immunofluorescence (IF). RT-PCR detected virus RNA in 79% of the patients at the time of admission, comparing favorably with IF, which detected antibodies in only 21% of the patients. Lassa virus RNA was detected by RT-PCR in all 29 patients by the third day of admission, whereas antibody was detectable by IF in only 52% of the patients. These results point to an important role for RT-PCR in the management of suspected cases of Lassa fever.

Base Sequence↗

LC16m8, a highly attenuated vaccinia virus vaccine lacking expression of the membrane protein B5R, protects monkeys from monkeypox.

The potential threat of smallpox as a bioweapon has led to the production and stockpiling of smallpox vaccine in some countries. Human monkeypox, a rare but important viral zoonosis endemic to central and western Africa, has recently emerged in the United States. Thus, even though smallpox has been eradicated, a vaccinia virus vaccine that can induce protective immunity against smallpox and monkeypox is still invaluable. The ability of the highly attenuated vaccinia virus vaccine strain LC16m8, with a mutation in the important immunogenic membrane protein B5R, to induce protective immunity against monkeypox in nonhuman primates was evaluated in comparison with the parental Lister strain. Monkeys were immunized with LC16m8 or Lister and then infected intranasally or subcutaneously with monkeypox virus strain Liberia or Zr-599, respectively. Immunized monkeys showed no symptoms of monkeypox in the intranasal-inoculation model, while nonimmunized controls showed typical symptoms. In the subcutaneous-inoculation model, monkeys immunized with LC16m8 showed no symptoms of monkeypox except for a mild ulcer at the site of monkeypox virus inoculation, and those immunized with Lister showed no symptoms of monkeypox, while nonimmunized controls showed lethal and typical symptoms. These results indicate that LC16m8 prevents lethal monkeypox in monkeys, and they suggest that LC16m8 may induce protective immunity against smallpox.

Animals↗

Viral infections in travellers from tropical Africa.

Examination of sera from 86 travellers to Britain from tropical Africa disclosed evidence of past infection with 10 identifiable viruses, of which the most important were O'nyong-nyong, dengue, chikungunya, and Ntaya. The findings indicate that infection with O'nyong-nyong may be acquired sporadically in Nigeria, Ghana, and Sierra Leone, where it has not previously been identified. Chikungunya infection had not been recorded in West Africa other than Nigeria and Senegal. Patients from Sierra Leone and contiguous Liberia had antibodies to this infection. An outbread of dengue fever in the Seychelles in early 1977 was confirmed. Ntaya virus, though known in Uganda, Cameroon, and Zaire, appears also to be transmitted in Kenya, Nigeria, and Zambia. Clinical studies indicated that chikungunya infection may present with alimentary features, possibly with jaundice. The clinical features of Ntaya infection may include kizarre neurological manifestations in addition to fever. The absence of Lassa antibodies among these travellers suggested that this infection is not a common hazard among such persons.

Adult↗

Seroepidemiology of human immunodeficiency virus in Africa.

Serum samples from 6015 African subjects without symptoms of the acquired immune deficiency syndrome (AIDS) or contact with the disease were examined for antibodies to the human immunodeficiency virus by a combination of an enzyme linked immunosorbent assay and radioimmunoprecipitation (2567 samples) or by immunofluorescence (3448 samples). Serum samples had been collected between 1976 and 1984 in Senegal (n = 789), Liberia (935), Ivory Coast (1195), Burkina Faso (299), Nigeria (536), Gabon (1649), Zaire (15), Uganda (164), and Kenya (433). Only four samples contained antibodies. Three of these were from attenders at the Lambarene clinic in Gabon and one from a villager in Senegal. By contrast, two out of six AIDS suspects from Guinea-Bissau, all 13 patients with AIDS from Kinshasa (Zaire), and two out of three of their contacts were seropositive, all these specimens having been collected in 1985. These data show that fewer than one in a 1000 subjects were seropositive for AIDS at the time of sampling before 1985 and do not support the hypothesis of the disease originating in Africa.

Africa↗

Behavioural diversity among the wild chimpanzee populations of Bossou and neighbouring areas, Guinea and Côte d'Ivoire, West Africa. A preliminary report.

We present a preliminary report on the differences and similarities in material culture among four neighbouring chimpanzee (Pan troglodytes verus) communities. One of these communities includes Bossou, a long-term field site of wild chimpanzees, in Guinea, West Africa. We also conducted surveys of three new sites. Two of those surveyed areas, Seringbara in Guinea and Yealé in Côte d'Ivoire, are located less than 12 km away from Bossou in the Nimba Mountains region, which forms a natural boundary between Guinea and Côte d'Ivoire. The third, Diécké, is situated further south-west, closer to the border with Liberia. During the surveys, we gathered behavioural information about these neighbouring populations of chimpanzees. The differences, as well as similarities, in material culture were tabulated based on our findings. The three behavioural variants found so far involve differences in nut cracking behaviour with regard to the species of nut cracked. Some variation in materials used for nut cracking has also been recorded. However, we still need to establish whether these local variations can be explained by the demands of the physical and biotic environments in which the populations of chimpanzees live. If these alternative hypotheses can be excluded with continuing research at the study sites, these differences are likely to be cultural behaviours that are influenced by the social context and mode, i.e. horizontal, vertical or oblique, of transmission, by the social structure and organisation of each community and/or perhaps by some form of social norms prevalent within these communities.

Animals↗

Genetic polymorphism of delta-aminolevulinate dehydrase in several population groups in Israel.

The genetic polymorphism of red cell delta aminolevulinate dehydrase (ALADH) has been investigated in several population groups in Israel: Ashkenazi Jews, non-Ashkenazi Jews from North Africa, Egypt, Turkey, Iraq, Iran, Yemen and the Balkans, and Arabs. The distribution of the ALADH genes was not homogeneous (chi 2 = 36.83; d.f. = 8; p less than 0.0005). A significantly higher frequency of the ALADH2 gene was observed among the Ashkenazi Jews (0.2021) than among the non-Ashkenazi Jews and Arabs (gene frequencies 0.0825-0.1290) or all the other population samples so far studied (Liberia, Japan, Italy, Germany and Spain).

Erythrocytes↗

Diagnosis of Strongyloides stercoralis in a peritoneal effusion from an HIV-seropositive man. A case report.

BACKGROUND: Strongyloides stercoralis, a nematode parasite in humans with free-living and autoinfective cycles, is often an asymptomatic infection of the upper small intestine. If the host becomes immunocompromised, autoinfection may increase the intestinal worm burden and lead to disseminated strongyloidiasis. The parthenogenetic adult female larvae can remain embedded in the mucosa of the small intestine for years, producing eggs that develop into either rhabditiform, noninfective larvae or filariform, infective larvae. Manifestations of dissemination occur when the filariform larvae penetrate the intestinal wall and migrate into the blood. Pulmonary involvement is common, and the central nervous system may be affected. Blood eosinophilia is typical, and gram-negative sepsis from enteric bacteria may occur. Much less commonly described is invasion of the peritoneal cavity with peritoneal effusion. CASE: A 49-year-old man who came to the United States from Liberia 4 years earlier presented with sudden onset of severe abdominal distention, generalized weakness and marked pedal edema. Diagnostic paracentesis showed numerous filariform larvae of S stercoralis. Stool examination confirmed the presence of both rhabditiform and filariform larvae. Subsequently the patient was found to be HIV seropositive, with a CD4 lymphocyte count of 59. CONCLUSION: Early detection of S stercoralis may alter the often-fatal course of infection. The present case is the second reported one in the English-language literature of the diagnosis of S stercoralis in ascitic fluid.

AIDS-Related Opportunistic Infections↗

Measuring total health inequality: adding individual variation to group-level differences.

BACKGROUND: Studies have revealed large variations in average health status across social, economic, and other groups. No study exists on the distribution of the risk of ill-health across individuals, either within groups or across all people in a society, and as such a crucial piece of total health inequality has been overlooked. Some of the reason for this neglect has been that the risk of death, which forms the basis for most measures, is impossible to observe directly and difficult to estimate. METHODS: We develop a measure of total health inequality - encompassing all inequalities among people in a society, including variation between and within groups - by adapting a beta-binomial regression model. We apply it to children under age two in 50 low- and middle-income countries. Our method has been adopted by the World Health Organization and is being implemented in surveys around the world; preliminary estimates have appeared in the World Health Report (2000). RESULTS: Countries with similar average child mortality differ considerably in total health inequality. Liberia and Mozambique have the largest inequalities in child survival, while Colombia, the Philippines and Kazakhstan have the lowest levels among the countries measured. CONCLUSIONS: Total health inequality estimates should be routinely reported alongside average levels of health in populations and groups, as they reveal important policy-related information not otherwise knowable. This approach enables meaningful comparisons of inequality across countries and future analyses of the determinants of inequality.

Journal Article↗

Genetic structuring and estimation of reproductive adults in Onchocerca volvulus: A genome-wide analysis across hosts and regions.

Genomic analysis of parasites can deepen our understanding of their transmission, population structure, and important biological characteristics. Onchocerciasis (river blindness), caused by the parasitic nematode Onchocerca volvulus, involves adult worms residing in subcutaneous nodules that produce larval-stage microfilariae (mf), which are routinely detected in the skin for diagnosis. Whole-genome studies of mf are limited; most analyses have focused on the mitochondrial genome. We conducted a genome-wide analysis with 94% median nuclear genome coverage, analyzing 171, 37, and 98 mf from 16, 3, and 5 individuals from Ghana, Liberia, and the Democratic Republic of Congo, respectively. These data were used to investigate population differentiation, estimate the number of reproductive adult worms, and analyze genetic variation across chromosomes. Population genetic analyses across hosts and countries showed that nuclear genome diversity can reveal fine-scale genetic structure, even between geographically close countries, providing more resolution than mitochondrial haplotype data. By reconstructing maternal and paternal sibships, we estimated the number of reproductively active adult filariae. Comparisons between adult worm estimates from genetic data and nodule observations showed that genetics-based estimates were higher or equal to observed worm counts in 8 out of 9 hosts for female worms and 7 out of 9 hosts for male worms. Our analysis also revealed lower-than-expected X chromosome diversity, consistent with neo-X chromosome fusions in filarial species. This study represents an important step in using nuclear genome data from mf to support onchocerciasis elimination efforts and in developing genetic tools that could inform mass drug administration programs.

Onchocerca volvulus↗

Dental caries of refugee children compared with US children.

OBJECTIVE: Dental care is a major unmet health need of refugee children. Many refugee children have never received oral health care or been exposed to common preventive oral health measures, such as a toothbrush, fluoridated toothpaste, or fluoridated water. Oral health problems among refugee children are most likely to be detected first by pediatricians and family practitioners. Given the increased influx of refugees into the United States, particularly children, it is important for the pediatric community to be aware of potential oral health problems among refugee children and be able to make referrals for treatment and recommendations for the prevention of future oral diseases. The purpose of this study was to describe the prevalence of caries experience and untreated decay among newly arrived refugee children stratified by their region of origin and compared with US children. METHODS: Oral health assessments were conducted within 1 month of arrival to the United States as part of the Refugee Health Assessment Program of the Massachusetts Department of Public Health. The outcome variables include caries experience and untreated decay. Caries experience is determined by the presence of an untreated caries lesion, a restoration, or a permanent molar tooth that is missing because it has been extracted as a result of dental caries. Untreated caries is detected when 0.5 mm of tooth structure is lost and there is brown coloration of the walls of the cavity. Comparisons of the refugee children with US children in Third National Health and Nutrition Examination Survey data were made using chi2 test of independence and multiple logistic regression. RESULTS: Oral health screenings were performed on 224 newly arrived refugees who ranged in age from 6 months to 18 years and had a mean age of 10.6 years (SD: 4.82; median: 10.7 years). African refugees represented 53.6%, with the majority from Somalia, Liberia, and Sudan. Eastern European refugees composed 26.8% of the study sample. The remaining 19.6% come from a number of countries, such as Afghanistan, Pakistan, and the Middle East. Refugee children had 51.3% caries experience and 48.7% with untreated decay. Caries experience in refugees varied by region of origin, with 38% from Africa exhibiting a history of caries compared with 79.7% of Eastern Europeans. The highest proportion of children with no obvious dental problems was from Africa (40.5%) compared with 16.9% from Eastern Europe. US children had caries experience similar to that of refugees (49.3%) but significantly lower risk of untreated decay (22.8%). Comparisons between refugee children and US children found significant differences for treatment urgency, untreated caries, extent of dental caries, and presence of oral pain. White refugee children, primarily from Eastern Europe, were 2.8 times as likely to have caries experience compared with white US children, with 9.4 times the risk of untreated decay compared with white US children. In contrast, African refugee children were only half as likely to have caries experience compared with white US children (95% confidence interval: 0.3-0.7) and African American children (95% confidence interval: 0.3-0.7). However, African refugee children were similar to African American children in risk of untreated decay (odds ratio: 0.94). CONCLUSION: African refugee children had significantly lower dental caries experience as well as fewer untreated caries as compared with similarly aged Eastern European refugee children. They were also less likely to have ever been to a dentist. Possible reasons for these findings may include differences in exposure to natural fluoride in the drinking water, dietary differences, access to professional care, and cultural beliefs and practices. The prevalence of caries experience and untreated caries differed significantly between refugee children and US children. These differences varied significantly by race. When refugee children were compared with US children, the African refugee children had only half the caries experience of either white or African American children. However, African refugee children had similar likelihood of having untreated caries as compared with African American children, despite that very few African children had previous access to professional dental care. These findings are consistent with previous studies on health disparities in the United States. White refugee children, primarily from Eastern Europe, were also 3 times as likely to have caries experience compared with either white or African American children and were 9.4 times as likely to have untreated caries as white US children. Refugee children are more likely to establish primary medical care before seeking dental treatment. With the limited access to dental care among refugees, pediatricians should be particularly alert to the risk of oral diseases among refugee children.

Adolescent↗

Random amplified polymorphic DNA (RAPD) analysis of Lutzomyia longipalpis laboratory populations.

The phlebotomine sand fly Lutzomyia longipalpis has been incriminated as a vector of American visceral leishmaniasis, caused by Leishmania chagasi. However, some evidence has been accumulated suggesting that it may exist in nature not as a single but as a species complex. Our goal was to compare four laboratory reference populations of L. longipalpis from distinct geographic regions at the molecular level by RAPD-PCR. We screened genomic DNA for polymorphic sites by PCR amplification with decamer single primers of arbitrary nucleotide sequences. One primer distinguished one population (Marajó Island, Pará State, Brazil) from the other three (Lapinha Cave, Minas Gerais State, Brazil; Melgar, Tolima Department, Colombia and Liberia, Guanacaste Province, Costa Rica). The population-specific and the conserved RAPD-PCR amplified fragments were cloned and shown to differ only in number of internal repeats.

Animals↗

Health issues in newly arrived African refugees attending general practice clinics in Melbourne.

OBJECTIVE: To identify the most common health issues diagnosed by general practitioners in newly arrived African refugees. DESIGN: Descriptive study based on a purposive sample of six GPs to collate data from medical records of patients from African countries who had attended their clinics for the first time between 1 January and 30 June 2005. SETTING: Two community health centres and two private general practices in metropolitan Melbourne. PARTICIPANTS: African refugee patients who arrived in Australia after 1 June 2004 and were seen by the six participating GPs between 1 January and 30 June 2005. MAIN OUTCOME MEASURES: Demographic characteristics, laboratory test results and final diagnoses. RESULTS: Data were collected from 258 patient files. Most patients were from Sudan (57%) or Liberia (17%). Half were aged under 15 years. The most common health problems identified were inadequate vaccinations, nutritional deficiencies (vitamin D and iron), infectious diseases (gastrointestinal infections, schistosomiasis, and latent tuberculosis) and dental disease. Musculoskeletal, psychological and social problems were common in adults. 37% of patients were tested for latent tuberculosis, and 25% of these tested positive. CONCLUSIONS: African refugees require comprehensive health assessments for undiagnosed and untreated health problems. While most of the common diseases identified are non-communicable, if left untreated they will affect the long-term health and productivity of new settlers.

Adolescent↗

History of U.S. military contributions to the study of malaria.

More so than any other infectious disease, malaria has all too often affected the conduct of military operations in war and in some cases has disproportionately influenced the outcome. From Napoleon's defensive action at Walcheren, to the Union Army's attempts to take control of the Mississippi River at Corinth and Vicksburg, to the dreadful numbers of malaria casualties suffered by U.S. Marines on the islands of Efate and Guadalcanal during World War II and more recently in Liberia in 2003, malaria has extracted a heavy toll. In this article, we summarize a few of the significant contributions to malaria control by U.S. military personnel throughout its history. We review examples of scientific achievements, medical breakthroughs, and lessons learned from preceding wars that continue to drive the quest for effective antimalarial therapies and preventive vaccines. This review is by no means comprehensive or complete but serves as a testament to the skill, courage, self-sacrifice, and devotion to duty of the many who have faithfully served their country in the past and to those today who continue the struggle against this disease.

Biomedical Research↗

Psychiatric referrals during peace and wartimes: a Nigerian experience.

Using a questionnaire administered by us, we sought to investigate the differences between patients referred to the psychiatric department of a Nigerian military general hospital during peacetime and those referred during the civil war in Liberia in which Nigerian soldiers were involved as peacekeepers. Referrals to psychiatry in peacetime were quite few but increased considerably during the period of combat in direct relation to the increase in the number of surgical wounded in action cases. Organic mental disorders and anxiety disorders were more frequently referred in peacetime than in war, whereas substance abuse disorders were more frequent during the combat period. Non-psychotic psychiatric conditions were less referred in the wartime group, partly because of nonrecognition at the mission areas and also because of recovery in front-line areas or consideration of their evacuation as a nonpriority. Mental health workers engaged at the mission areas require more training in the identification of such cases.

Adolescent↗

[Cholera in Guinea: the 1994-1995 epidemic].

Since the first outbreak in 1970, cholera epidemics have occurred regularly in Guinea. Until 1994, epidemics recurred every 8 years and were confined to the capital and coastal areas. The first cases in every epidemic were observed in coastal lagoons near the Sierra Leone border. In 1994, the disease demonstrated its migratory ability as the first cases were reported in towns located in far eastern inland areas. Spread of the disease from war-torn Sierra Leone and Liberia where epidemics have also been reported cannot be ruled out. Control measures have gradually been implemented to deal with these outbreaks and a treatment facility was built at the University of Conakry in 1994. Bacteriological studies including antibiotic susceptibility tests carried out at this center showed that the offending bacteria was Vibrio cholerae El Tor of the Ogawa group. Although this strain is relatively sensitive to all antibiotics, analysis of epidemiological data revealed high mortality rates at the beginning of every outbreak probably due to delays in organizing appropriate care. A major effort is now being made to improve the response time particularly in remote inland areas.

Cholera↗