Introduction Spleen and liver play a decisive role in Plasmodium vinckei malaria by clearing the parasitized red blood cells from the circulation (4, 16). It has previously been observed that both organs show a pronounced accumulation of macrophages (9, 12), accompanied by an increase of phagocytic activity (13) and an elevated production of reactive oxygen intermediates (3, 12) in malaria. Since immunity in murine malaria seems to be T cell dependent, involving both antibody and cell mediated mechanisms (2, 6, 8), it was of interest to study the changes in the T cell population of spleen and liver during P. vinckei malaria. In this paper, we have analysed the variation of mouse equivalent CD3, CD4, and CD8 positive T lymphocytes in both organs, by using immunohistochemistry and flow cytometry techniques.

BACKGROUND:The Toll-like receptors (TLRs) mediate innate immunity to various pathogens. A mutation (S180L) in the TLR downstream signal transducer TIRAP has recently been reported to be common in Europeans and Africans and to roughly half the risks of heterogeneous infectious diseases including malaria, tuberculosis, bacteremia, and invasive pneumococal disease in heterozygous mutation carriers.METHODS:We assessed the TIRAP S180L variant by melting curve and RFLP analysis in 1095 delivering women from malaria-endemic Ghana, as well as in a further 1114 individuals participating in case control studies on sepsis and leprosy in Germany, Turkey and Bangladesh.RESULTS:In Ghana, the TIRAP S180L polymorphism was virtually absent. In contrast, the mutation was observed among 26.6%, 32.9% and 12% of German, Bangladesh and Turkish controls, respectively. No significant association of the heterozygous genotype with sepsis or leprosy was observed. Remarkably, homozygous TIRAP 180L tend to increase the risk of sepsis in the German study (P = 0.04).CONCLUSION:A broad protective effect of TIRAP S180L against infectious diseases per se is not discernible.

ABSTRACT Intermittent preventive treatment in infants with sulfadoxine-pyrimethamine (IPTi-SP) reduces malaria episodes by 20 to 59% across Africa. This protective efficacy, however, may be affected by the high frequency of malnutrition in African infants. We analyzed the impact of malnutrition as defined by anthropometry on the incidence of malaria and on the protective efficacy of IPTi in a cohort of 1,200 children in northern Ghana, where malaria is hyperendemic. These children received IPTi-SP or placebo at 3, 9, and 15 months of age and were monitored until 24 months of age. Malnutrition was present in 32, 40, and 50% of children at ages 3, 9, and 15 months, respectively. It was associated with increased risks of severe anemia and death but not an increased risk of malaria. Although malaria slightly contributed to chronic malnutrition, IPTi did not substantially improve child growth. Importantly, the protective efficacies of IPTi in malnourished children were roughly half or even less of those observed in nonmalnourished children. In the first year of life, IPTi reduced the incidence of malaria to a significantly lesser extent in infants who received both doses in a malnourished condition (25%; 95% confidence interval [CI], −7 to 48%) compared to that of nonmalnourished children (46%; 95% CI, 30 to 58%; P = 0.049). Moreover, in contrast to nutritionally advantaged children, the rate of severe malaria appeared to be increased in malnourished children who took IPTi. IPTi might exhibit reduced efficacy in regions of abundant malnutrition. Concomitant nutrition programs may be needed in these places to achieve the desired impact.

: Recurrent fever lasting for nine months up to ten years occurred in seven women and three men, with fever of up to 39 degrees C lasting from two to seven days. All patients had travelled outside of Germany at least one year previously. Micro-Widal reaction revealed antibodies against Yersinia enterocolitica (serotype 0:3 or 0:9), with a titre of between 1:80 and 1:1280. Antibiotic treatment (doxycycline or cotrimoxazole) brought cure in all ten. The antibody titres fell in seven of nine patients; titres could not be followed in one.

Use of intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) during pregnancy (IPTp-SP) has become policy in much of sub-Saharan Africa but crucially depends on the efficacy of SP. We assessed the frequency of the dhfr triple mutation among Plasmodium falciparum isolates obtained from pregnant Ghanaian women in 1998, 2000, and 2006. The prevalence of the triple mutation, which confers resistance to SP, doubled from 36% to 73% during the study period (P<.001). In 2006, the prevalence was virtually identical among women of early gestation and delivering women with or without a history of IPTp-SP use, indicating that such treatment did not select for mutant parasites. Nevertheless, IPTp-SP may be outdated by drug resistance before it is fully implemented.

Viral gastrointestinal infections are among the most important causes of childhood morbidity and mortality, especially in non-industrialized countries. The objective of this study was the molecular characterization of rotaviruses, noroviruses, adenoviruses, astroviruses, and enteroviruses obtained from 367 children in the Northern Region of Ghana. One hundred and forty-two rotavirus-positive stool samples were examined. The most frequent type identified was G1P[8] occurring in 80% of the cases. Of 27 norovirus positive samples, 5 isolates belonged to genogroup I and 22 to genogroup II. Adenoviruses were detected in 73 samples; 23.3% of these belonged to genogroup F, 31.5% to D, 17.8% to A, 15.1% to C, and 12.3% to B. Astrovirus typing of 12 positive samples displayed a distribution into four different genotypes: five sequences clustered with AstV-8, four with AstV-2, two with AstV-5, and one with AstV-6. Twenty-three different enterovirus types were identified in 45 positive samples, coxsackievirus A24 being the most frequent pathogen (18%). This first, comprehensive molecular characterization of enteric viruses in northern Ghana provides baseline data for the molecular epidemiology of these pathogens and immunisation strategies. The available rotavirus vaccines cover the predominant G1P[8] type and would reduce substantially disease burden in that area.

OBJECTIVESInformation on antimicrobial susceptibility of bacterial pathogens is scarce in resource-poor settings. We determined the susceptibility of bacterial enteric pathogens and faecal Escherichia coli isolates obtained from children in urban Tamale, Northern Ghana, to antibiotics widely used in the that area [ampicillin or amoxicillin, trimethoprim/sulfamethoxazole (SXT) and chloramphenicol] and to alternative drugs.METHODSFive Shigella spp., 6 Salmonella spp. and 318 E. coli were isolated from stool specimens obtained from 367 children with or without acute diarrhoea. Isolates were differentiated using standard laboratory procedures and tested using a breakpoint microbroth dilution method for their susceptibility to 18 antimicrobials and by disc diffusion for their susceptibility to chloramphenicol.RESULTSAlthough the salmonellae showed an acceptable resistance pattern, E. coli isolates and the closely related shigellae were highly resistant. About 91% and 81% of E. coli isolates from patients or controls, respectively, were resistant to ampicillin (MICs > or = 8 mg/L), 88% and 76% to trimethoprim/sulfamethoxazole (MICs > or = 80/4 mg/L) and 46% and 41% to chloramphenicol (inhibition zones < or = 12 mm). Resistance to beta-lactam antibiotics or chloramphenicol was observed more frequently among isolates obtained from infants when compared with older children (1-4 years of age).CONCLUSIONSEnteric bacteria from children in urban Northern Ghana are highly resistant to antibiotics used in that area. Therefore, new antibiotics should be introduced for the treatment of infections caused by these bacteria. Additionally, the establishment of a surveillance of the prevalence of the main bacterial infectious agents and their antimicrobial resistance is desirable.

Mannose-binding lectin (MBL) is a serum protein which initiates innate immune responses to microbial pathogens by binding to non-self surface oligosaccharides. MBL deficiency is the most common congenital immunodeficiency of human and has been shown to predispose to infections, particularly in children and immune compromised. In a matched case-control study among 870 Ghanaian children, we examined the influence of six polymorphisms of the MBL2 gene on Plasmodium falciparum infection and severe malaria. A missense mutation resulting in low MBL activity (MBL2*C) was found in 35% of healthy controls, but in 42% of asymptomatically infected children (P=0.01), and in 46% of patients with severe malaria (P=0.007). Heterozygosity for MBL2*C was associated with increased odds of infection (odds ratio (OR), 1.6; 95% confidence interval (CI), 1.1–2.1), severe malaria (OR, 1.7; 95% CI, 1.2–2.4), and of severe anemia in particular (OR, 2.3; 95% CI, 1.4–3.8). The population attributable fraction of severe malaria cases attributable to MBL2*C heterozygosity was 17%. Our results suggest that the MBL pathway of the complement system is a critical determinant of both, susceptibility to P. falciparum infection and manifestation of severe malaria, particularly in young children in whom specific immune responses are weak or absent.

Amodiaquine/artesunate and artemether/lumefantrine are currently implemented as antimalarial drugs in Africa. In this study, we assessed Plasmodium falciparum pfmdr1 alleles suggesting reduced sensitivity to amodiaquine/artesunate (86Y-184Y-1246Y) and artemether/lumefantrine (184F and 86N-184F-1246D) in 111 African isolates imported to Germany between 1997 and 2005. pfmdr1 86Y-184Y-1246Y occurred less frequently in West African isolates (2.5%) than in East African parasites (45.8%) (P<0.001) and less frequently in infections contracted in countries currently implementing amodiaquine/artesunate (5.7%) compared with countries with an artemether/lumefantrine policy (20.8%) (P=0.03). pfmdr1 184F showed an opposite pattern. pfmdr1 alleles reveal significant differences between West and East Africa, supporting the current implementation of first-line antimalarials.

Despite widespread resistance, chloroquine remains widely used in West Africa, particularly in home treatment. We examined chloroquine blood levels on admission to a referral hospital with respect to the manifestation of severe malaria in 290 Ghanaian children. Of the patients, 78% exhibited chloroquine concentrations (subtherapeutic, 35%; therapeutic, 37%; supratherapeutic, 6%) and 11% died. Most parasites (78%) carried the pfcrt-T76 chloroquine resistance mutation. High drug concentrations correlated with reduced parasitaemia but also with selection of resistant parasites, lower respiratory and heart rates, increased plasma lactate levels and impaired consciousness. Geometric mean chloroquine concentrations tended to be higher in children who died than in survivors (1.135 vs. 778 nmo/l; P = 0.09). Supratherapeutic drug levels (>5000 nmol/l) were associated with fatal outcome (odds ratio 8.6; 95% CI 1.4-51.7). Residual chloroquine concentrations were found to be abundant in children with severe malaria and to be associated with alterations in the clinical manifestation of the disease and its case fatality. This may result from toxic effects of the drug and/or reflect preceding overtreatment in children with acute life-threatening disease. In areas of intense chloroquine resistance and frequent pre-treatment, additional administration of chloroquine at hospital admission is not only ineffective but may even further endanger patients. (C) 2007 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

ABSTRACT Morbidity and mortality from malaria remain unacceptably high among young children in sub-Saharan Africa. Intermittent preventive treatment in infancy (IPTi) involves the administration of antimalarials alongside routine vaccinations and might be an option in malaria control. In an area of intense, perennial malaria transmission in northern Ghana, 1,200 children received IPTi with sulfadoxine-pyrimethamine or placebo at approximately 3, 9, and 15 months of age. Children were followed up until 24 months of age to assess morbidity and adverse events. During the intervention period (3 to 18 months of age), IPTi reduced the incidences of malaria and severe anemia by 22.5% (95% confidence interval, 12 to 32%) and 23.6% (95% confidence interval, 4 to 39%), respectively, and reduced hospitalizations and episodes of asymptomatic parasitemia by one-third. Protection was pronounced in the first year of life and not discernible in the second. The malaria-protective effect was largely confined to a period of 1 month after sulfadoxine-pyrimethamine treatments. Following the intervention, protection against asymptomatic parasitemia persisted. In contrast, a significant rebound of severe malaria, predominantly severe malarial anemia, occurred among children having received IPTi. Although the treatment was generally well tolerated, one case of moderately severe skin reaction followed sulfadoxine-pyrimethamine treatment. IPTi reduces malaria and anemia in infants in northern Ghana. Extension of IPTi into the second year of life by administering a dose at 15 months of age provided no substantial benefit beyond a 1-month prophylactic effect. Although this simple intervention offers one of the few available malaria-preventive measures for regions where malaria is endemic, the observed rebound of severe malaria advises caution and requires further investigation.

After liver transplantation for hepatitis-B-related diseases, patients currently receive lifelong treatment with hepatitis B immunoglobulin to prevent endogenous reinfection with hepatitis B virus (HBV). Active immunization with hepatitis B vaccine would be a preferable alternative; however, most attempts to immunize these patients with standard vaccine have failed. A recent study with a new adjuvanted hepatitis B vaccine was exceptionally successful, leading to a high-titered long-lasting antibody response in 80% of all vaccinees. To identify the immunological mechanisms behind these unexpected results, the successfully vaccinated participants were tested for hepatitis B surface antigen (HBsAg)-specific T and B cells, and their cellular responses to revaccination with conventional vaccine were studied. HBsAg-specific CD4(+) T lymphocytes could be detected in 13 of 16 patients after immunization with the new vaccine. Unexpectedly, these T cells produced almost exclusively interleukin (IL)-10 and had a CD4(+)/CD25(+) phenotype. They were functionally active, suppressing cytokine secretion in HBsAg-specific (Th1) cells, thus representing antigen-specific regulatory T cells (T(Reg)). Following a booster dose with conventional vaccine 22-31 months after completion of the initial vaccination series, the T-cell pattern in the revaccinated individuals changed substantially: 7 days after revaccination 9 of 11 individuals showed a switch to a Th1-type immune response with HBsAg-specific T cells secreting IL-2, interferon gamma and tumor necrosis factor alpha as observed in healthy controls. Four weeks after the booster, 4 patients still showed a Th1-type cytokine pattern, whereas in 5 patients only IL-10-secreting cells were detectable. After 1 year, in 3 of 4 revaccinated individuals only IL-10-secreting cells could be found, whereas the specific T cells of the fourth patient still showed a Th1-type of response. HBsAg-specific T(Reg) cells could be demonstrated in HBV-positive liver transplant recipients successfully immunized with a new adjuvanted vaccine. Revaccination led to immediate disappearance of the these cells and the appearance of HBsAg-specific T cells with a Th1-type cytokine profile, which in most cases were replaced by the IL-10-secreting regulatory cells during the following months. The specific induction of T(Reg) cells could contribute to the poor response of liver transplant recipients to conventional vaccine. In conclusion,, for successful vaccination of these patients, a vaccine with a strong inhibitory effect on T(Reg) cells would be desirable.

ABSTRACT Placental sequestration of Plasmodium falciparum in pregnancy may impair the usefulness of molecular markers of sulfadoxine-pyrimethamine resistance. In 300 infected, delivering women, the concordance of PCR-restriction fragment length polymorphism-derived parasite resistance alleles in matched samples from placenta and circulation was 83 to 98%. Sulfadoxine-pyrimethamine resistance typing in peripheral blood is reasonably representative of P. falciparum infecting pregnant women.

ABSTRACT We evaluated the Rida Quick rotavirus/adenovirus Combi rapid immunochromatographic test (ICT) under field conditions with Ghanaian children with acute diarrhea. Compared to PCR results, sensitivities and specificities were 75% and 95% for rotavirus and 22% and 84% for adenovirus. In resource-poor settings, ICTs may help to overcome difficulties in the diagnosis of rotavirus infection.

Acute diarrhoea is a major cause of childhood morbidity and mortality in sub-Saharan Africa. Its microbiological causes and clinico-epidemiological aspects were examined during the dry season 2005/6 in Tamale, urban northern Ghana.