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PubMed1994

Gene trees and hominoid phylogeny.

Here we present a DNA sequence study that incorporates intraspecific variation from all five genera of hominoids (apes and humans). Recently it has been claimed that using single individuals to analyze species' relationships might be misleading if within-species variation is great. Our results indicate that despite high intraspecific variation in mitochondrial cytochrome oxidase subunit II gene sequences of some hominoids, humans and chimpanzees are nonetheless significantly most closely related. We also report the observation that variation within the gorilla species exceeds that between common and pygmy chimpanzee species, a finding with implications for conservation. In contrast, humans are less mitochondrially diverse than lowland gorillas inhabiting western Africa.

Animals↗

PubMedDate not supplied

A 13-week feeding study in the rat with shea oleine and hardened shea oleine.

Shea oleine is an oil fraction derived from the nut of the tree, Butyrospermum parkii, which grows in central and western Africa. There are several uses of shea oleine, including its use as a cooking oil and, after hardening, in margarine and toffee fat. As part of a series of studies, a 13-week rat feeding study was conducted in which groups of Colworth-Wistar rats (15 male and 15 female) were fed 27.5% total fat semipurified diets containing 20% (w/w) shea oleine (SU) or hardened shea oleine (SH). Equivalent groups of rats were fed either 20% (w/w) palm oil (PU), soyabean oil (BU), or the hardened (hydrogenated) equivalents (PH and BH, respectively). Assessments of body weight, food and water intake, clinical pathology, organ weights, and macroscopic histopathology were carried out. Results showed that shea oleine diets produced similar biological effects to palm oil and and soyabean oil diets. A slightly reduced body weight gain was noted in rats fed either of the shea oleine diets in comparison with palm oil and soyabean oil. The process of hardening had no significant impact on the normal growth in rats fed shea oleine, although minor differences compared with unhardened diets comprised some small changes in clinical chemistry parameters, raised liver weight, and less liver lipid. In addition, raised alkaline phosphatase and an increase in food intake were noted in rats fed SH. All diets were well tolerated in the growing rat and none of the findings in the study were considered to be adverse.

Alkaline Phosphatase↗

PubMed2003

Molecular systematic analysis reveals cryptic tertiary diversification of a widespread tropical rain forest tree.

The broad geographic range of many Neotropical rain forest tree species implies excellent dispersal abilities or range establishment that preceded the formation of current dispersal barriers. In order to initiate historical analyses of such widespread Neotropical trees, we sequenced the nuclear ribosomal spacer (ITS) region of Symphonia globulifera L. f. (Clusiaceae) from populations spanning the Neotropics and western Africa. This rain forest tree has left unmistakable Miocene fossils in Mesoamerica (15.5-18.2 Ma) and in South America ( approximately 15 Ma). Although marine dispersal of S. globulifera is considered improbable, our study establishes three marine dispersal events leading to the colonization of Mesoamerica, the Amazon basin, and the West Indies, thus supporting the paleontological data. Our phylogeographic analysis revealed the spatial extent of the three Neotropical S. globulifera clades, which represent trans-Andes (Mesoamerica+west Ecuador), cis-Andes (Amazonia+Guiana), and the West Indies. Strong phylogeographic structure found among trans-Andean populations of S. globulifera stands in contrast to an absence of ITS nucleotide variation across the Amazon basin and indicates profound regional differences in the demographic history of this rain forest tree. Drawing from these results, we provide a historical biogeographic hypothesis to account for differences in the patterns of beta diversity within Mesoamerican and Amazonian forests.

Africa↗

PubMed2005

Reemergence of monkeypox: prevalence, diagnostics, and countermeasures.

Human monkeypox is a viral zoonotic disease that occurs mostly in the rain forests of central and western Africa. However, the disease recently emerged in the United States in imported wild rodents from Africa. Monkeypox has a clinical presentation very similar to that of ordinary forms of smallpox, including flulike symptoms, fever, malaise, back pain, headache, and characteristic rash. Given this clinical spectrum, differential diagnosis to rule out smallpox is very important. There are no licensed therapies for human monkeypox; however, the smallpox vaccine can protect against the disease. The discontinuation of general vaccination in the 1980s has given rise to increasing susceptibility to monkeypox virus infection in the human population. This has led to fears that monkeypox virus could be used as a bioterrorism agent. Effective prevention relies on limiting the contact with infected patients or animals and limiting the respiratory exposure to infected patients.

Animals↗

PubMed2006

Mycobacterium africanum elicits an attenuated T cell response to early secreted antigenic target, 6 kDa, in patients with tuberculosis and their household contacts.

BACKGROUND: Mycobacterium africanum, a member of the M. tuberculosis complex that is infrequently found outside of western Africa, is the cause of up to half of the tuberculosis cases there. METHODS: We genotyped mycobacterial isolates obtained from a study of patients with tuberculosis and their household contacts and compared T cell responses and tuberculin skin test results by infecting genotype. RESULTS: The T cell response to early secreted antigenic target, 6 kDa (ESAT-6), was attenuated in patients with tuberculosis (odds ratio [OR], 0.41 [95% confidence interval {CI}, 0.19-0.89]; P = .024) and household contacts (OR, 0.56 [95% CI, 0.38-0.83]; P = .004) infected with M. africanum, compared with the response in those infected with M. tuberculosis. In these same groups, responses to culture filtrate protein, 10 kDa (CFP-10), were nonsignificantly attenuated (P = .22 and P = .16, respectively), as were tuberculin skin test results (P = .30 and P = .46, respectively). Sequencing of region of difference 1 of M. africanum revealed that Rv3879c is a pseudogene in M. africanum; however, this finding does not provide an obvious mechanism for the attenuated ESAT-6 response. CONCLUSIONS: This is the first evidence, to our knowledge, that strain differences affect interferon- gamma -based T cell responses. Our findings highlight the need to test new diagnostic candidates against different strains of mycobacteria. Integrating additional immunologic and genomic comparisons of M. tuberculosis and M. africanum into further studies may provide fundamental insights into the interactions between humans and mycobacteria.

Adolescent↗

PubMed2005

CTX-M-15 extended-spectrum (beta)-lactamase from Nigerian Klebsiella pneumoniae.

OBJECTIVES: In this study, extended-spectrum beta-lactamases (ESBLs) were characterized from 30 selected multidrug-resistant Klebsiella pneumoniae strains isolated from patients with community-acquired urinary tract infections from Southwest Nigeria. METHODS: The beta-lactamases were phenotypically characterized using isoelectric focusing, genotypically characterized using PCR assays and hybridization of the PCR products. Two of the bla(CTX-M) genes were completely sequenced. The location of the CTX-M-type genes was determined using transformation, DNA-DNA hybridization, PCR assays and hybridization of the PCR products from the Escherichia coli transformants. RESULTS: All 30 isolates produced at least one beta-lactamase. Seventeen of the isolates were resistant to cefotaxime, and had > or =100-fold reduction in susceptibility with cefotaxime plus clavulanic acid (4 mg/L), indicating the presence of an ESBL. The 17 isolates were shown to have bla(CTX-M) genes that were associated with large plasmids (> or =58 kb), which also carried a tetracycline resistance gene, tet(A), and various aminoglycoside resistance genes. Two CTX-M-type genes were sequenced and had amino acid sequences indistinguishable from previously sequenced CTX-M-15 beta-lactamases. The ISEcp1 element was located upstream of bla(CTX-M-15) in the same position as previously described. In addition, 23 of the isolates produced TEM beta-lactamases, 27 produced SHV beta-lactamases and four produced AmpC beta-lactamases. CONCLUSIONS: Thirty K. pneumoniae produced multiple beta-lactamases, with 57% producing CTX-M enzymes. This is the first characterization of CTX-M-15-positive K. pneumoniae in Western Africa.

Anti-Bacterial Agents↗

PubMed1995

Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group.

BACKGROUND: Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries. There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation. PURPOSE: Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types. METHODS: More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries. Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics. We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types. A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity. RESULTS: HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries. HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5%. HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common. There was significant geographic variation in the prevalence of some less common virus types. A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America. In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors). CONCLUSIONS: Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide. They also suggest that most genital HPVs are associated with cancer, at least occasionally. IMPLICATION: The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs.

Adult↗

PubMed1987

Stochastic model for interhuman spread of monkeypox.

With the eradication of smallpox, systematic routine vaccination with vaccinia has ceased and an increasing proportion of the human population in tropical rain forest areas of central and western Africa lacks vaccinia-derived immunity to monkeypox virus. This raises the question of the ability of monkeypox virus to establish and maintain itself in an unvaccinated population through continuous man-to-man transmission. A computerized stochastic model of Monte Carlo type was constructed to assess this potential risk. Simulated series were repeated 100 times to obtain distributions of predicted outcomes for decreasing levels of vaccination coverage (70 per cent, 50 per cent, and 0 per cent). The results revealed a substantial increase in new secondary cases in the total absence of vaccinia-induced immunity. Nevertheless, none of the simulated series did lead to an "explosive" epidemic. The model clearly indicated diminishing numbers of cases in successive generations and eventual cessation of transmission. Therefore, it appears highly improbable that the virus could maintain itself permanently in communities by interhuman transmission. After the eradication of smallpox, human monkeypox constitutes the most important orthopoxvirus infection in man, but analysis of information collected up to this time suggests that it does not represent currently a serious public health problem or a challenge to the achieved eradication of smallpox.

Adolescent↗

PubMed2004

Whooping cough metapopulation dynamics in tropical conditions: disease persistence and impact of vaccination.

Recent insights in compiling metapopulation models and infectious disease dynamics have enabled a better understanding of spatial and temporal persistence of diseases. The concept of the critical community size (CCS) has been developed with major consideration on analyses of whooping cough and measles dynamics from temperate countries for which large datasets are available. However, few studies have questioned the generality of CCS curves for other regions, i.e. tropical areas, mainly because data are very sparse. This work constitutes, to our knowledge, the first study of whooping cough persistence in a tropical area, in a rural part of Senegal (Western Africa) where the population has been followed for 20 years. In this small community, the CCS is not reached even if we observe CCS-like curves showing persistence increasing with population size. In addition, our analysis supports the idea that vaccination has impacted the spatiotemporal dynamics and persistence of the disease. These findings suggest the need for more comparative analyses of spatio-temporal data series from a wide range of contrasted countries, for example developed and developing nations, so as to have a better understanding of vaccination effects on disease dynamics and persistence.

Humans↗

PubMed2005

Novel vacuolate sulfur bacteria from the Gulf of Mexico reproduce by reductive division in three dimensions.

Large spherical sulfur bacteria, 180-375 microm in diameter, were found regularly and in abundance in surface sediments collected from hydrocarbon seeps (water depth 525-640 m) in the Gulf of Mexico. These bacteria were characterized by a thin 'shell' of sulfur globule-filled cytoplasm that surrounded a central vacuole (roughly 80% of biovolume) containing high concentrations of nitrate (average 460 mM). Approximately 800 base pairs of 16S rRNA gene sequence data, linked to this bacterium by fluorescent in situ hybridization, showed 99% identity with Thiomargarita namibiensis, previously described only from sediments collected off the coast of Namibia (Western Africa). Unlike T. namibiensis, where cells form a linear chain within a common sheath, the Gulf of Mexico strain occurred as single cells and clusters of two, four and eight cells, which were clearly the product of division in one to three planes. In sediment cores maintained at 4 degrees C, which undoubtedly experienced a diminishing flux of hydrogen sulfide over time, the Thiomargarita-like bacterium remained viable for up to 2 years. During that long period, each cell appeared to undergo (as judged by change in biovolume) one to three reductive divisions, perhaps as a dispersal strategy in the face of diminished availability of its putative electron donor.

Bacterial Proteins↗

PubMed2000

Maternal morbidity and mortality in two different populations of Senegal: a prospective study (MOMA survey).

OBJECTIVE: To compare maternal morbidity and mortality in two urban populations with contrasting availability of health care, and to test the hypothesis that differences in maternal outcome result mainly from the management of delivery in health facilities. DESIGN: A population-based study of a cohort of pregnant women which was part of a multicentre study of maternal morbidity in six countries of western Africa (MOMA). SETTING: Two different urban areas of Senegal (Saint-Louis and Kaolack). POPULATION: 3,777 pregnant women who were followed up throughout pregnancy, delivery and puerperium. MAIN OUTCOME MEASURES: Maternal morbidity and mortality: morbidity was assessed from women's recall at each visit by the investigator and from obstetric complications diagnosed by the birth attendant within health facilities. RESULTS: Maternal mortality was higher in the Kaolack area where women gave birth mainly in district health care centres, usually assisted by traditional birth attendants, than in Saint-Louis where women giving birth in health facilities went principally to the regional hospital and were usually assisted by midwives (874 and 151 maternal deaths per 100,000 live births, respectively, P < 0 x 01). Maternal morbidity, however, was higher in Saint-Louis than in Kaolack area, especially for births in health facilities (9 x 50 and 4 x 84 episodes of obstetric complications per 100 live births, respectively, P < 0 x 01). Univariate and multivariate analyses showed that morbidity was mainly associated with the training of the birth attendant in facility deliveries and that antenatal care had no effect. CONCLUSION: Midwives in health facilities appear to detect more obstetric complications than traditional birth attendants. Immediate detection leads to immediate care and to low fatality rates. This could explain differences in maternal outcome between two urban centres with contrasting health care availability. These results suggest that one of the strongest weapons in the fight against maternal mortality is the employment of the most qualified personnel possible for monitoring labour.

Adult↗

PubMed1997

Usefulness of Semen Microscopy in the Diagnosis of a Difficult Case of Schistosoma haematobium Infection in a Returned Traveler.

Schistosoma haematobium is endemic in many countries of Southeast Asia, eastern and western Africa, and South America. It affects mainly the urinary system, although infection of the genital organs is not infrequent.1,2 Infection of male genital organs, especially of the seminal vesicles and prostate1,3 may result in hematospermia and infertility.2,4,5,6,7,8,9 The diagnosis of Schistosoma haematobium traditionally relies on demonstrating the presence of characteristic ova in urine and, less often, in feces. Serology is nonspecific and lacks sensitivity because the antigens utilized in the indirect hemagglutination assay are derived from Schistosoma mansoni. In addition, serology cannot differentiate past from recently acquired infection. We report a case of Schistosoma haematobium infection in a returned traveler in whom numerous ova were detected in semen despite repeated negative urinary and fecal examinations and negative serology.

Journal Article↗

PubMed2000

Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures.

Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga (Apocynaceae family), a rain forest shrub that is native to western Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and thirst, and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and opiates. Anecdotal reports attest that a single dose of ibogaine eliminates opiate withdrawal symptoms and reduces drug craving for extended periods of time. The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. The majority of ibogaine biotransformation proceeds via CYP2D6, including the O-demethylation of ibogaine to 12-hydroxyibogamine (noribogaine). Blood concentration-time effect profiles of ibogaine and noribogaine obtained for individual subjects after single oral dose administrations demonstrate complex pharmacokinetic profiles. Ibogaine has shown preliminary efficacy for opiate detoxification and for short-term stabilization of drug-dependent persons as they prepare to enter substance abuse treatment. We report here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification. Self-reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge. Because ibogaine is cleared rapidly from the blood, the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine on the central nervous system.

Adult↗

PubMed2001

Simian immunodeficiency virus infections in vervet monkeys (Clorocebus aethiops) at an Australian zoo.

A number of monkey species, including African green monkeys and African vervet monkeys (Chlorocebus aethiops), are frequently infected in the wild and in captivity with a Simian immunodeficiency virus strain, SIVagm, a primate lentivirus. Up to 50% of African green monkeys are estimated to be infected with SIVagm. SIV strains are very closely related to HIV-2 strains, which are a cause of AIDS in humans, predominantly in western Africa, although cases in Australia have also been reported. It is generally thought that SIV is non-pathogenic in several natural hosts, including African green monkeys. Nevertheless many SIV strains induce a profound immunodeficiency virtually identical to HIV-1 induced AIDS in humans when administered to Asian macaque species such as rhesus (Macaca mulatta) or pigtailed macaques (M nemestrina). SIV infection of Asian macaque species is frequently employed as an animal model for AIDS vaccine studies. In November 1996 a group of 10 African vervet monkeys were imported from the USA for display at Victoria's Open Range Zoo in Werribee. Two animals in this group of monkeys later developed a fatal gastroenteric illness. These diagnoses led us to initiate SIV testing of the colony.

Animals↗

PubMed2001

Protective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer.

Buruli ulcer, caused by Mycobacterium ulcerans, is characterized by deep and necrotizing skin lesions, mostly on the arms and legs. Together with tuberculosis and leprosy, this mycobacterial disease has become a major health problem in tropical and subtropical regions, particularly in central and western Africa. No specific vaccine is available for Buruli ulcer. There is, however, evidence in the literature that suggests a cross-reactive protective role of the tuberculosis vaccine M. bovis BCG. To identify potential mechanisms for this cross-protection, we identified and characterized the M. ulcerans homologue of the important protective mycobacterial antigen 85 (Ag85A) from BCG. The homologue is well conserved in M. ulcerans, showing 84.1% amino acid sequence identity and 91% conserved residues compared to the sequence from BCG. This antigen was sufficiently conserved to allow cross-reactive protection, as demonstrated by the ability of M. ulcerans- infected mice to exhibit strong cellular immune responses to both BCG and its purified Ag85 complex. To further address the mechanism of cross-reactive protection, we demonstrate here that prior vaccination with either BCG or plasmid DNA encoding BCG Ag85A is capable of significantly reducing the bacterial load in the footpads of M. ulcerans- infected mice, as determined by Ziehl-Neelsen staining and by actual counting of CFU on 7H11 Middlebrook agar. Together, the results reported here support the potential of a cross-protective Ag85-based future vaccine against tuberculosis, Buruli ulcer, and leprosy.

Amino Acid Sequence↗

PubMed1992

Circumsporozoite genotyping of global isolates of Plasmodium vivax from dried blood specimens.

The prevalence and global distribution of two circumsporozoite (CS) genotypes of Plasmodium vivax (VK210 and VK247) were determined by genetic analysis of isolates from 234 malaria-infected patients. Whole blood specimens were collected on filter paper from patients infected with malaria in Thailand, Mexico, Papua New Guinea, Peru, Afghanistan (Pakistan), India, and western Africa and from 50 asymptomatic smear-negative controls. Following extraction of DNA from the filter paper samples, the CS gene was amplified by the polymerase chain reaction and genotyped by using oligoprobes specific for the VK210 and VK247 repeat epitopes. The sensitivity of genotyping from a single blood dot was 95.2%. The VK247 CS genotype was identified in the blood of patients from all seven study areas and was the predominant form present in samples from Thailand (83%) and Papua New Guinea (90%). In contrast, VK247 DNA was present in only 9% of isolates from Mexico. Individuals infected with both genotypes simultaneously were identified in all study areas except Mexico and were particularly common in Thailand (58%) and Papua New Guinea (60%). These findings indicate that the VK247 genotype of P. vivax is widely distributed but that its prevalence varies geographically. In addition, we conclude that use of samples of whole blood on filter paper is a practical and sensitive method for determining the genotypes of large numbers of malaria isolates collected in field settings.

Amino Acid Sequence↗

PubMed2006

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↗

PubMed2000

Characterization of human CD4(+) T-cell clones recognizing conserved and variable epitopes of the Lassa virus nucleoprotein.

T cells must play the major role in controlling acute human Lassa virus infection, because patients recover from acute Lassa fever in the absence of a measurable neutralizing antibody response. T cells alone seem to protect animals from a lethal Lassa virus challenge, because after experimental vaccination no neutralizing antibodies are detectable. In order to study human T-cell reactivity to single Lassa virus proteins, the nucleoprotein (NP) of Lassa virus, strain Josiah, was cloned, expressed in Escherichia coli, and affinity purified. Peripheral blood mononuclear cells (PBMC) obtained from 8 of 13 healthy, Lassa virus antibody-positive individuals living in the Republic of Guinea, western Africa, were found to proliferate in response to the recombinant protein (proliferation index >/=10). PBMC obtained from one individual with a particularly high proliferative response were used to generate 50 NP-specific T-cell clones (TCC). For six of these the epitopes were mapped with overlapping synthetic peptides derived from the sequence of the NP. These CD4(+) TCC displayed high specific proliferation and produced mainly gamma interferon upon stimulation with NP. Because variation of up to 15% in the amino acid sequences of the structural proteins of naturally occurring Lassa virus variants has been observed, the reactivity of the TCC with peptides derived from the homologous epitopes of the Nigeria strain of Lassa virus and of the eastern Africa arenavirus Mopeia was tested. With the Nigeria strain of Lassa virus the levels of homology were 100% for two of these epitopes and 85% for three of them, whereas homology with the respective Mopeia epitopes ranged from 92 to 69%. Reactivity of the TCC with peptides derived from the variable epitopes of the Nigeria strain and of Mopeia was reduced or completely abolished. This report shows for the first time that seropositive individuals from areas of endemicity have very strong memory CD4(+) T-cell responses against the NP of Lassa virus, which are partly strain specific and partly cross-reactive with other Lassa virus strains. Our findings may have important implications for the strategy of designing recombinant vaccines against this mainly T-cell-controlled human arenavirus infection.

Adolescent↗