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Biomedical subjects

M R Rao

Publications and source records attributed to M R Rao.

At least 19 recordsLinked to original sources

Effect of breastfeeding on cognitive development of infants born small for gestational age.

UNLABELLED: Breastfeeding during infancy appears to result in enhanced cognitive development during childhood, but it is not known whether breastfeeding should be encouraged for infants born small for gestational age (SGA) whose growth might otherwise benefit from nutritional supplementation. To address this issue, duration of exclusive breastfeeding and cognitive development were evaluated prospectively for 220 term children born SGA and 299 term children born appropriate for gestational age (AGA). Cognitive development was assessed using the Bayley Scale of Infant Development at 13 mo and Wechsler Preschool and Primary Scales of Intelligence at 5 y of age. Infants born SGA were given supplemental foods significantly earlier than those born AGA. Growth of infants born SGA was not related to early nutritional supplementation. The salutary effect of exclusive breastfeeding on cognitive development was greater for children born SGA than for those born AGA. Based on a linear association between duration of exclusive breastfeeding and intelligence quotient (IQ), children born SGA and exclusively breastfed for 24 wk were predicted to have an 11-point IQ advantage over those breastfed for 12 wk, as opposed to a 3-point advantage for children born AGA with similar durations of breastfeeding. The IQ distribution of children born SGA and exclusively breastfed for more than 12 wk was not different from that of all children born AGA. CONCLUSION: Duration of exclusive breastfeeding has a significant impact on cognitive development without compromising growth among children born SGA. These data suggest that mothers should breastfeed exclusively for 24 wk to enhance cognitive development.

Breast Feeding↗

Investigations into the safety and immunogenicity of a killed oral cholera vaccine developed in Viet Nam.

OBJECTIVE: To evaluate a killed oral cholera vaccine produced in Viet Nam, and to compare the Vietnamese vaccine with one that is licensed internationally. METHOD: Two-dose regimens of a locally produced, bivalent, anti-O1, anti-O139 killed oral whole-cell cholera vaccine (biv-WC) and of a commercially available, monovalent (anti-O1) oral recombinant B subunit-killed whole-cell cholera vaccine (rBS-WC) were compared in two trials in Viet Nam. In the first trial, 144 adults were randomized to biv-WC with or without buffer, rBS-WC with buffer, or placebo without buffer. In the second, 103 children aged 1-12 years were randomized to biv-WC without buffer, rBS-WC with buffer, or placebo without buffer. FINDINGS: No regimen was associated with significant side-effects. In adults, ca 60% of recipients of either vaccine exhibited at least fourfold serum anti-O1 vibriocidal antibody responses and ca 40% of recipients of biv-WC demonstrated anti-O139 vibriocidal responses. Both anti-O1 (ca 90% in each vaccine groupand anti-O139 (68% in the biv-WC group) vibriocidal responses occurred more frequently in children. The responses to biv-WC were unaffected by the receipt of buffer. CONCLUSION: It was concluded that biv-WC was safe and immunogenic, that it could be administered without buffer, and that it could elicit robust immune responses even in children, for whom the risk of endemic cholera is highest.

Administration, Oral↗

Pathogenicity and convalescent excretion of Campylobacter in rural Egyptian children.

Campylobacter infection in developing countries has not received much public health attention because of the observation that infections are not associated with disease beyond the first 6 months of life. A cohort of 397 Egyptian children aged less than 3 years, who were observed twice weekly during 1995--1998, experienced an incidence of 0.6 episodes of Campylobacter diarrhea per child-year. A total of 13% of the Campylobacter diarrheal episodes were characterized by severe dehydration. Age-specific incidence rates (episodes per year) were 0.9 in infants aged less than 6 months, 1.5 in those 6--12 months, and 0.4 and 0.2 in the second and third years of life, respectively. Convalescent excretion of Campylobacter after a diarrheal episode might be enhancing transmission and contributing to this high incidence. Observed risk factors for Campylobacter diarrhea were poor hygienic conditions and the presence of animals in the house. Regardless of the child's age, a first infection by Campylobacter was associated with diarrhea (odds ratio = 2.45; 95% confidence interval: 1.61, 3.71); however, subsequent infections were associated with diarrhea only in children aged less than 6 months. This observation that natural infection did not confer protection during the first 6 months of life poses a challenge to vaccine development.

Age Distribution↗

Cost of immunization with a locally produced, oral cholera vaccine in Viet Nam.

Policy decisions regarding whether to incorporate new vaccines into routine public health practice in developing countries will depend in part on the costs of vaccine purchase and of vaccine delivery. In March, 1997, a large-scale effectiveness trial of a locally produced, orally administered bivalent vaccine against Vibrio cholerae 01 and 0139 began in Viet Nam. Empirical data obtained from the trial was used to determine the costs of the immunization campaign from the government perspective. The study population, including the children less than one year of age and pregnant women who were ineligible for immunization, was 353926. A total of 289041 persons received two doses of vaccine, and 13340 persons received one dose of vaccine. Two-dose vaccine coverage was 83.4%. The total cost of vaccine delivery during the immunization campaign was $66527. The cost of each dose of vaccine was $0.31. Therefore, the total cost of the immunization campaign was $0.44 per dose administered, and $0.91 per fully immunized person. Attempts to reduce the cost per dose of vaccine (e.g. the use of a monovalent vaccine against serogroup 01) are likely to have a large impact on the cost of future similar immunization campaigns.

Administration, Oral↗

Epidemiology of postshigellosis persistent diarrhea in young children.

BACKGROUND: Dysentery accounts for 20% of the 4.6 million diarrhea-associated deaths among children in developing countries, with the risk from death in dysenteric persistent diarrhea 10-fold higher than that in acute dysentery. Although Shigella accounts for the majority of dysenteric episodes, very little is known about the epidemiology of postshigellosis persistent diarrhea. METHODS: Rural Bangladeshi children younger than 5 years of age (n = 1,756) were followed for 1 month after exposure to sentinel cases of Shigella dysentery. The likelihood of an acute diarrheal episode becoming persistent was assessed. RESULTS: Diarrhea caused by Shigella was significantly associated with an increased risk of persistent diarrhea (age-adjusted relative risk, 1.83; 95% confidence interval, 1.19 to 2.81). Despite the use of nalidixic acid in dysenteric episodes, persistent diarrhea occurred in 23% of children with shigellosis. Infection by multiply antibiotic-resistant Shigella isolates (age-adjusted relative risk, 3.76; 95% confidence interval, 1.51 to 9.36) and occurrence of shigellosis during infancy were observed to be risk factors for initiation of Shigella diarrhea persistence. However, 88% of the persistent shigellosis episodes occurred in older children, 50% were associated with nondysenteric shigellosis and 79% were caused by Shigella species other than Shigella dysenteriae 1. CONCLUSIONS: These data demonstrate the importance of Shigella as a cause of persistent diarrhea and indicate that strategies to prevent postshigellosis persistent diarrhea must be broad-based, with a focus on older children as well as infants, management of nondysenteric as well as dysenteric disease and prevention of diarrhea caused by multiple Shigella species.

Bangladesh↗

Induction of systemic antifimbria and antitoxin antibody responses in Egyptian children and adults by an oral, killed enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine.

We assessed serologic responses to an oral, killed whole-cell enterotoxigenic Escherichia coli plus cholera toxin B-subunit (ETEC-rCTB) vaccine in 73 Egyptian adults, 105 schoolchildren, and 93 preschool children. Each subject received two doses of vaccine or placebo 2 weeks apart, giving blood before immunization and 7 days after each dose. Plasma antibodies to rCTB and four vaccine-shared colonization factors (CFs) were measured by enzyme-linked immunosorbent assay. Immunoglobulin A (IgA) antibodies to rCTB and CFA/I were measured in all subjects, and those against CS1, CS2, and CS4 were measured in all children plus a subset of 33 adults. IgG antibodies to these five antigens were measured in a subset of 30 to 33 subjects in each cohort. Seroconversion was defined as a >2-fold increase in titer after vaccination. IgA and IgG seroconversion to rCTB was observed in 94 to 95% of adult vaccinees, with titer increases as robust as those previously reported for these two pediatric cohorts. The proportion showing IgA seroconversion to each CF antigen among vaccinated children (range, 70 to 96%) and adults (31 to 69%), as well as IgG seroconversion in children (44 to 75%) and adults (25 to 81%), was significantly higher than the corresponding proportion in placebo recipients, except for IgA responses to CS2 in adults. IgA anti-CF titers peaked after one dose in children, whereas in all age groups IgG antibodies rose incrementally after each dose. Independently, both preimmunization IgA titer and age were inversely related to the magnitude of IgA responses. In conclusion, serologic responses to the ETEC-rCTB vaccine may serve as practical immune outcome measures in future pediatric trials in areas where ETEC is endemic.

Administration, Oral↗

Fructose, 1,6-diphosphate mitigates CCl4 suppressed nitric oxide synthase activity in rats.

Effect of fructose 1,6-diphosphate (FDP) and carbon tetrachloride (CCl4) were studied individually and in combination on rat endothelial (ET) and smooth muscle cell (SMC) nitric oxide synthase (NOS) activities in vivo, inhibition of ET and SMC NOS activity in CCl4 treated rats was reversed in FDP + CCl4 treated animals. Cellular based NOS activity was significantly increased in FDP treated group of rats when compared to non treated controls. The results suggest a significant increase in NOS in rats treated with a combination of FDP + CCl4 thus overcoming the suppression of NOS exposed to CCl4 alone.

Animals↗

High concentration of glucose inhibits endothelium-dependent vasorelaxation of rabbit aortic artery.

AIM: To determine whether high concentration of glucose inhibits endothelium-dependent vasorelaxation of rabbit aortic artery and possible mechanisms. METHODS: The organ-bath of rings of rabbit aorta was used to determine changes of tension of vessel in response to different concentrations of acetylcholine (ACh) and sodium nitroprusside (SNP) after removal of endothelium, coincubated with nitric oxide synthase (NOS) inhibitor L-NMMA, different concentrations of glucose, vitamin C, and cell-permeable superoxide dismutase-mimetic and oxygen-derived free radical scavenger manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP). RESULTS: ACh induced concentration- and endothelium-dependent aortic vasorelaxation. High concentration of glucose markedly inhibited this vasorelaxation, and vitamin C and MnTMPyP could not antaganize this inhibitory effect by high concentrations of glucose. SNP induced concentration-dependent and endothelium-independent vasorelaxation, and high concentration of glucose had no effect on the vasorelaxation by SNP. CONCLUSION: High concentration of glucose inhibited endothelium-dependent vasorelaxation and this effect was unlikely mediated through activating oxygen-derived free radical production.

Animals↗

[Effects of praeruptorin C on vascular hypertrophy, [Ca2+]i, collagen content and NO in renovascular and spontaneously hypertensive rats].

AIM: To study the effects of praeruptorin C (pra-C), a pure constituent isolated from "Qian-Hu", the roots of Peucedanum praeruptorum Dunn. (Umbelliferae), on vascular hypertrophy, collagen content, transient [Ca2+]i, NO and vascular response of the thoracic aorta of renovascular and spontaneously hypertensive rats (RHR, SHR). METHODS: RHR and SHR were given pra-C 20 mg.kg-1.d-1 for 9 weeks, ig. Blood pressure of both rats were measured using tail cuff manometry. Under inverted microscopy the length and width of the smooth muscle cells were measured by using computer software MICC (Dongnan University). [Ca2+]i of smooth muscle cell (SMCs) was measured with Fura-2/AM. By measuring the specific aminoacid hydroxyproline content, the collagen content was obtained. By using Griess reagent, the NO in the smooth muscle cells (SMCs) was measured. RESULTS: The intermedia of the thoracic aorta in RHR was enlarged than that of the normal and pra-C groups. The size (length x width) of the SMCs of thoracic aorta from RHR increased 73.4 microns vs nomal 34.5 microns and pra-C 34 microns. The collagen content of thoracic aorta was 39% +/- 6.8% dry weight in RHR, they were 26.5% +/- 3% dry weight in normal and 25.6% +/- 1.1% dry weight in pra-C, RHR vs pra-C. The resting [Ca2+]i of single cell of SMCs was (62 +/- 6) nmol.L-1. In Hanks solution containing CaCl2 1 mmol.L-1, the resting [Ca2+]i of SMCs was (150 +/- 8) nmol.L-1 in normal. (226 +/- 11) nmol.L-1 in RHR. In presence of KCl 60 mmol.L-1, NE 10 mumol.L-1, ANG II 100 nmol.L-1 and ATP 30 mumol.L-1 the [Ca2+]i of SMCs were increased by 128%; 132%; 233% and 152% in RHR, respectively. The pra-C group was similar to the normal group. The resting [Ca2+]i of SMCs was (71 +/- 6) nmol.L-1 in control of SHR, in Hanks solution containing CaCl2 1 mmol.L-1. The resting [Ca2+]i of SMCs was (160 +/- 8) nmol.L-1 in normal, and (362 +/- 18) nmol.L-1 in SHR. In presence KCl 60 mmol.L-1 and NE 10 mumol.L-1 the [Ca2+]i of SMCs were increased by 235% and 200% in SHR, respectively. Pra-C group was similar to normal group. NO of SMCs was decreased 76% in SHR, pra-C group was nearly normal. The pra-C improved vascular responses of the thoracic aorta of RHR. CONCLUSION: These results indicate that pra-C improved the vascular hypertrophy by decreasing the size of SMCs cells, collagen content. SMCs [Ca2+]i and increasing NO production.

Animals↗

[Depressive effect of tetrandrine on collagen synthesis in vascular smooth muscle cells].

AIM: To clarify whether collagen deposition and collagen synthesis are increased in renovascular hypertensive rats (RHR) and whether these are affected by treatment with tetrandrine (Tet). METHODS: Collagen deposition was detected by electron microscope and evaluated by the amount of hydroxyproline in aorta of sham-operated rats (Sham), renovascular hypertensive rats (RHR), and Tet treated RHR. The aortic vascular smooth muscle cells (AVSMCs) were isolated and cultured. The collagen synthesis in cultured AVSMCs was detected by [3H]-proline incorporation. RESULTS: The ultrastructure of aorta suggests that AVSMCs in RHR had been transferred from contractile phenotype to synthetic phenotype. Compared with sham-operated rats, the hydroxyproline content in aorta was increased by 36.6% in RHR, while it was reduced by 18.7% in Tet treated RHR (P < 0.01, vs RHR). Tet (0.1-10 mumol.L-1) treatment in vitro induced a concentration dependent depression [3H]-proline incorperation stimulated by NE or Ang II in AVSMCs from either Sham or RHR. CONCLUSION: The depressive effects of tetrandrine on collagen synthesis and deposition in arteries may contribute to the regression of vascular remodeling.

Alkaloids↗

Identification of two novel zinc finger modules and nuclear localization signal in rat spermatidal protein TP2 by site-directed mutagenesis.

Spermatidal protein TP2, which appears transiently during stages 12-16 of mammalian spermiogenesis, is a DNA condensing zinc metalloprotein with a preference to GC-rich DNA. We have carried out a detailed site-directed mutagenesis analysis of rat spermatidal protein TP2 to delineate the amino acid residues involved in coordination with two atoms of zinc. Two zinc fingers modules have been identified involving 4 histidine and 4 cysteine residues, respectively. The modular structure of the two zinc fingers identified in TP2 define a new class of zinc finger proteins that do not fall into any of the known classes of zinc fingers. Transfection experiments with COS-7 cells using wild type and the two zinc finger pocket mutants have shown that TP2 preferentially localizes to nucleolus. The nuclear localization signal in TP2 was identified to be (87)GKVSKRKAV(95) present in the C-terminal third of TP2 as a part of an extended NoLS sequence.

Amino Acid Sequence↗

Astrovirus diarrhea in Egyptian children.

This study describes the epidemiology of astrovirus diarrhea among a population-based cohort of 397 children aged <3 years residing in rural Egypt from 1995 to 1998. The age-specific incidence rates of astrovirus diarrheal episodes per person-year were 0.38 for infants aged <6 months, 0.40 for those aged 6-11 months, 0.16 for those aged 12-23 months, and 0.05 for those aged 24-35 months. The overall incidence rate of astrovirus diarrhea was the same as that of rotavirus diarrhea, 0.19 episodes per person-year. Astrovirus infection was pathogenic and associated with severe dehydration in 17% of the cases. The most frequent serotype was HAstV-1, and, in order of decreasing frequency, HAstV-5, HAstV-8 and HAstV-3, HAstV-6, HAstV-4, and HAstV-2. In determining whether astrovirus diarrhea was associated with a reduced incidence of subsequent disease, there was evidence to suggest HAstV-1 homotypic immunity but not heterotypic immunity. Because we observed 38% of the incidence of astrovirus diarrhea to occur in infants aged <6 months, a candidate astrovirus vaccine would have to confer immunity very early in life.

Astroviridae Infections↗

Seroepidemiology of Helicobacter pylori infection in a population of Egyptian children.

BACKGROUND: To describe the seroepidemiology of Helicobacter pylori infection in a population of Egyptian children under 3 years. METHODS: A cohort of children under 36 months, residing in Abu Homos, Egypt, were visited at home twice weekly. Information regarding the child's breastfeeding status was obtained, and periodic anthropometric and household hygiene surveys were performed. In June 1997, a serosurvey was conducted on 187 study participants over 6 months old. The serosurvey was repeated in October 1997. All sera were tested for IgG antibodies to H. pylori. RESULTS: The June prevalence of H. pylori infection was 10%, and the incidence from June to October was 15%. Between June and October, 8 (42%) of 19 children that were positive for H. pylori infection seroreverted to negative. All seroreversions occurred in children 6-17 months. Other than age, no sociodemographic or environmental factor was significantly associated with incident H. pylori infection. There was no significant differences in the weight-for-age, weight-for-height, and height-for-age z-scores between children with and without prevalent H. pylori infection. CONCLUSIONS: Infection with H. pylori is common in Egyptian children under 3 years old and is not associated with malnutrition. No predictors for H. pylori infection were found. Our preliminary evidence for transient H. pylori infections in young children needs to be confirmed in a prospective cohort study, and predictors for persistent infection should be sought, since only these may be relevant to the known sequellae of infection.

Anthropometry↗

Alterations of amino acid levels from striatum, hippocampus, and cerebral cortex induced by global cerebral ischemia in gerbil.

AIM: To investigate global cerebral ischemia-induced alterations in the levels of glutamate, aspartate, gamma-aminobutyric acid (GABA), glutamine, glycine, and taurine from hippocampus, striatum, and cerebral cortex in gerbils. METHODS: The gerbil global cerebral ischemia model was prepared by bilateral carotid artery occlusion; the contents of amino acids were assayed using high performance liquid chromatography (HPLC) combined with fluorescent detection after precolumn derivatization. RESULTS: After the ligation of bilateral carotid artery for 5 min and reperfusion for 60 min, the contents of glutamate from hippocampus, striatum, and cortex in gerbils were increased by 40%, 49%, and 67%, respectively. Similarly, the global cerebral ischemia resulted in increase by 80%, 69%, and 83% of aspartate contents in hippocampus, striatum, and cortex, respectively. Moreover, the same treatment also induced significant increases in the contents of GABA, glutamine, glycine, and taurine from various brain regions in gerbils. Furthermore, pretreatment with ketamine (120 mg/kg, i.p.) reversed ischemia-evoked increases of glutamate, aspartate, glycine, and glutamine in hippocampus, striatum, and cortex of gerbils. However, administration of ketamine (120 mg/kg, i.p.) markedly suppressed but not abolished the ischemia-induced increases of taurine and GABA from hippocampus, striatum, and cortex in gerbils. CONCLUSION: The increases of glutamate, aspartate, glycine, and glutamine induced by acute global cerebral ischemia may constitute the biochemical basis of ischemic brain damage. Correspondingly, the release of GABA and taurine may be an important self-protective mechanism. Ketamine may protect neurons against ischemic insult by inhibiting global cerebral ischemia-evoked increase of glutamate, glycine, and aspartate.

Animals↗

Cloning of rat MLH1 and expression analysis of MSH2, MSH3, MSH6, and MLH1 during spermatogenesis.

The mismatch repair system has been highly conserved in various species. In eukaryotic cells, the Mut S and Mut L homologues play crucial roles in both DNA mismatch repair and meiotic recombination. A full-length rat cDNA clone for rat MLH1 has been constructed using the RT-PCR method. The cDNA has an open reading frame of 2274 nucleotides for a protein of 757 amino acids. We have also obtained partial cDNA clones for MSH3 and MSH6. Northern blot analysis of rat MLH1, MSH2, MSH3, and MSH6 in the testes of rats of different ages showed differential expression of these genes as a function of developmental maturation of the testes. The expression analysis suggests that MSH3 may have a more predominant role in the meiotic recombination process.

Adaptor Proteins, Signal Transducing↗

Epidemiology of rotavirus diarrhea in Egyptian children and implications for disease control.

Reliable epidemiologic data are essential for formulating effective policy to control rotavirus disease through immunization. The objective of this study was to describe the epidemiology of rotavirus diarrhea in a population-based cohort of children under 3 years of age residing in Abu Homos, Egypt, in 1995-1996. Rotavirus diarrhea incidence rates (episodes per person-year) were 0.13 for infants aged <6 months, 0.61 for those aged 6-11 months, 0.17 for those aged 12-23 months, and 0.15 for those aged 24-35 months. Fifty-six percent of children with rotavirus diarrhea had clinical dehydration; 90% of rotavirus diarrheal episodes occurred between July and November. In infants under 1 year of age, receipt of breast milk was associated with a lower incidence of rotavirus diarrhea. No other sociodemographic or environmental factor was found to be significantly associated with rotavirus diarrhea. Of 46 rotavirus isolates with strains identified, 41 (89%) were G serotypes 1 and 2. Rotavirus diarrhea was a major cause of morbidity in this cohort. Promotion of breastfeeding may exert a protective effect in young infants in this setting, but improvements in water and sanitation are unlikely to be effective preventive measures. The use of effective immunization against rotavirus in early infancy should be considered a public health priority.

Age Distribution↗

Lamellarin alpha 20-sulfate, an inhibitor of HIV-1 integrase active against HIV-1 virus in cell culture.

HIV-1 integrase is an attractive target for anti-retroviral chemotherapy, but to date no clinically useful inhibitors have been developed. We have screened diverse marine natural products for compounds active against integrase in vitro and found a series of ascidian alkaloids, the lamellarins, that show selective inhibition. A new member of the family named lamellarin alpha 20-sulfate (1), the structure of which was determined from spectroscopic data, displayed the most favorable therapeutic index. The site of action of lamellarin alpha 20-sulfate on the integrase protein was mapped by testing activity against deletion mutants of integrase. Inhibition of isolated catalytic domain was detectable though weaker than inhibition of full length integrase; possibly lamellarin alpha 20-sulfate binds a site composed of multiple integrase domains. Lamellarin alpha 20-sulfate also inhibited integration in vitro by authentic HIV-1 replication intermediates isolated from infected cells. Lamellarin alpha 20-sulfate was tested against wild type HIV using the MAGI indicator cell assay and found to inhibit early steps of HIV replication. To clarify the inhibitor target, we tested inhibition against an HIV-based retroviral vector bearing a different viral envelope. Inhibition was observed, indicating that the HIV envelope cannot be the sole target of lamellarin alpha 20-sulfate in cell culture. In addition, these single round tests rule out action against viral assembly or budding. These findings provide a new class of compounds for potential development of clinically useful integrase inhibitors.

Animals↗

Characterization of unusual G8 rotavirus strains isolated from Egyptian children.

We report the first detection of P[14], G8 rotaviruses isolated in Egypt from the stool of children participating in a 3 year study of rotavirus epidemiology. Two strains, EGY1850 and EGY2295, were characterized by a serotyping enzyme immunoassay (EIA), virus neutralization, and sequence analysis of the genes encoding VP7 and the VP8* portion of the VP4 gene. These two strains shared a high level of homology of their VP7s (87.8% nucleotide [nt], 97.2% amino acid [aa]) and VP4s (89.6% nt, 97.1% aa) and had the highest VP7 identity to serotype G8 (> 82% nt, > 92% aa) and VP4 identity to genotype P[14] (> or = 81% nt, > 91% aa) strains. Serological results with a VP7 G8-specific and VP4 P[14]-specific neutralizing monoclonal antibodies supported the genetic classification of EGY1850 and EGY2295 as P[14], G8. Genogroup analysis supports earlier findings that human G8 rotaviruses may be genetically related to bovine rotaviruses. These findings demonstrate that our understanding of the geographic distribution of rotavirus strains is incomplete, emphasize the need to monitor rotavirus serotypes, and extend the known distribution of serotype G8 and genotype P[14] strains in Africa.

Animals↗