Christian G. Meyer

Plasma interleukin-10 :tumor necrosis factor (TNF)-α ratio is associated with TNF promoter variants and predicts malarial complications

In individuals with severe malarial anemia, plasma levels of tumor necrosis factor (TNF)-alpha tend to exceed those of interleukin (IL)-10. In this study, IL-10:TNF plasma level ratios <1 were found to be a risk factor for both cerebral malaria and severe anemia (P=.009), whereas higher IL-10:TNF ratios were observed more frequently in hyperparasitemic individuals. When considering allelic variants of the TNF promoter in children with severe malaria, carriers of the wild type more frequently had an IL-10:TNF ratio >1 (P=.008). In contrast, individuals with a mutation at position -238 of the TNF promoter (TNF(-238A) and TNF(-376A/-238A)) consistently had lower IL-10 than TNF plasma levels (IL-10:TNF ratio <1; P=.003). Our results show that, in children with severe malaria, TNF promoter variants influence the balance of IL-10:TNF in the plasma, which, in turn, affects the outcome in terms of clinical complications.

Red cell glucose-6-phosphate dehydrogenase status and pyruvate kinase activity in a Nigerian population

Summary Glucose‐6‐phosphate dehydrogenase A− (G6PD A−) deficiency is a common enzymopathy in Africa that sporadically leads to manifest haemolytic anaemia. It is not exactly known how far the haematological status of individuals with either homozygous or heterozygous G6PD A− deficiency differs from that of individuals with normal G6PD activity. In a field study in Nigeria, we determined G6PD gene variants, the corresponding G6PD and pyruvate kinase (PK) activities, and basic haematological parameters in clinically healthy individuals, who were, in part, asymptomatically infected by malaria parasites. Red blood cell counts and haemoglobin levels were lower in G6PD A− deficient than in G6PD normal subjects. PK activities were higher in G6PD deficients, indicating a younger red cell population in these individuals. These findings suggest that G6PD A− deficiency is accompanied by chronic subclinical haemolysis. As a consequence, the reduced life span of red cells leads to an impaired diagnosis of G6PD heterozygosity when applying routine biochemical methods.

Impact of subpatent multi-species and multi-clonal plasmodial infections on anaemia in children from Nigeria

Childhood anaemia in sub-Saharan Africa is often caused by Plasmodium falciparum malaria. The influence of subpatent, multi-species and polyclonal infections with malaria parasites on haematological parameters was assessed in 1996/97 in clinically healthy children in Nigeria. Of the 228 children studied, 64% were anaemic by the WHO age-dependent criteria. A univariate analysis of risk factors indicated that the prevalence of anaemia was dependent on the number of Plasmodium species detected by species-specific PCR (P < 0.0001). Furthermore, the prevalence of anaemia increased gradually with the complexity (P < 0.003) as well as with the extent of P. falciparum parasitaemia (P < 0.0001). A logistic regression analysis revealed that individuals with an enlarged spleen tended to be anaemic. The number of Plasmodium species by which an individual was infected was independently associated with anaemia (P < 0.03). ANOVA revealed that the age-corrected values for haemoglobin (Hb) and red blood cells (RBCs) were mainly influenced by the occurrence of mixed infections. Haematological parameters were also influenced by the number of different P. falciparum clones by which an individual was infected. Hb levels and RBC counts were further diminished by additional infections with P. malariae and/or P. ovale. However, the effect of multi-species infections on haematological parameters exceeded that of multi-clonal infections.

Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study

Summary Background Available incidence data for invasive salmonella disease in sub-Saharan Africa are scarce. Standardised, multicountry data are required to better understand the nature and burden of disease in Africa. We aimed to measure the adjusted incidence estimates of typhoid fever and invasive non-typhoidal salmonella (iNTS) disease in sub-Saharan Africa, and the antimicrobial susceptibility profiles of the causative agents. Methods We established a systematic, standardised surveillance of blood culture-based febrile illness in 13 African sentinel sites with previous reports of typhoid fever: Burkina Faso (two sites), Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar (two sites), Senegal, South Africa, Sudan, and Tanzania (two sites). We used census data and health-care records to define study catchment areas and populations. Eligible participants were either inpatients or outpatients who resided within the catchment area and presented with tympanic (≥38·0°C) or axillary temperature (≥37·5°C). Inpatients with a reported history of fever for 72 h or longer were excluded. We also implemented a health-care utilisation survey in a sample of households randomly selected from each study area to investigate health-seeking behaviour in cases of self-reported fever lasting less than 3 days. Typhoid fever and iNTS disease incidences were corrected for health-care-seeking behaviour and recruitment. Findings Between March 1, 2010, and Jan 31, 2014, 135 Salmonella enterica serotype Typhi (S Typhi) and 94 iNTS isolates were cultured from the blood of 13 431 febrile patients. Salmonella spp accounted for 33% or more of all bacterial pathogens at nine sites. The adjusted incidence rate (AIR) of S Typhi per 100 000 person-years of observation ranged from 0 (95% CI 0–0) in Sudan to 383 (274–535) at one site in Burkina Faso; the AIR of iNTS ranged from 0 in Sudan, Ethiopia, Madagascar (Isotry site), and South Africa to 237 (178–316) at the second site in Burkina Faso. The AIR of iNTS and typhoid fever in individuals younger than 15 years old was typically higher than in those aged 15 years or older. Multidrug-resistant S Typhi was isolated in Ghana, Kenya, and Tanzania (both sites combined), and multidrug-resistant iNTS was isolated in Burkina Faso (both sites combined), Ghana, Kenya, and Guinea-Bissau. Interpretation Typhoid fever and iNTS disease are major causes of invasive bacterial febrile illness in the sampled locations, most commonly affecting children in both low and high population density settings. The development of iNTS vaccines and the introduction of S Typhi conjugate vaccines should be considered for high-incidence settings, such as those identified in this study. Funding Bill & Melinda Gates Foundation.

The contribution of alpha+-thalassaemia to anaemia in a Nigerian population exposed to intense malaria transmission.

Summary The proportion to which α‐thalassaemia contributes to anaemia in Africa is not well recognized. In an area of intense malaria transmission in South‐West Nigeria, haematological parameters of α‐thalassaemia were examined in 494 children and 119 adults. The –α3.7 type of α+‐thalassaemia was observed at a gene frequency of 0.27. Nine and 36.5% of individuals were homozygous and heterozygous, respectively. P.falciparum‐infection was present in 78% of children and in 39% of adults. The α‐globin genotypes did not correlate with the prevalence of P. falciparum‐infection. α+‐thalassaemic individuals had significantly lower mean values of haemoglobin, mean corpuscular volume, and mean corpuscular haemoglobin than non‐thalassaemic subjects. Anaemia was seen in 54.7% of children with a normal α‐globin genotype, in 69.9% of heterozygous (odds ratio: 1.99, 95% confidence interval: 1.32–3.00, P= 0.001), and in 88.4% of homozygous α+‐thalassaemic children (odds ratio: 7.72, 95% confidence interval: 2.85–20.90, P= 0.0001). The findings show that α+‐thalassaemia contributes essentially to mild anaemia, microcytosis, and hypochromia in Nigeria.

Plasmodium falciparum Infection: Influence on Hemoglobin Levels in α-Thalassemia and Microcytosis

Plasmodium falciparum malaria, alpha-thalassemia, and anemia are frequent in African children. In 494 nonhospitalized Nigerian children, P. falciparum infection rates, alpha-globin genotypes, and hematologic parameters were determined. P. falciparum infection was observed in 78% of the children. The gene frequency of alpha-thalassemia was 0.28. Infection rates and parasitemia were similar for the 3 alpha-globin genotypes. In contrast to nonthalassemic and heterozygous persons, infection in children with homozygous alpha-thalassemia did not influence hemoglobin values. Because microcytosis and anemia are common features of alpha-thalassemia, their significance in P. falciparum infection was examined. Microcytosis was significantly associated with protection from hemoglobin decrease due to P. falciparum. Moreover, the rate of infection was lower in microcytic than in normocytic anemia.

Labrets in Africa and Amazonia: medical implications and cultural determinants

The custom of wearing labrets has a long tradition. Labrets appeared independently several thousand years ago in various culture groups in Asia, Europe, Africa and the Americas. Today, apart from diverse body modifications as increasingly practiced in western civilisations, lip plates and plugs are found among a small number of tribal groups only in Africa and Amazonia. We summarise the history of labrets in different societies, describe medical consequences of wearing lip plates and plugs for jaws and teeth and address relevant cultural issues.

Clinical utility of an optimised multiplex real-time PCR assay for the identification of pathogens causing sepsis in Vietnamese patients

INTRODUCTION For the identification of bacterial pathogens, blood culture is still the gold standard diagnostic method. However, several disadvantages apply to blood cultures, such as time and rather large volumes of blood sample required. We have previously established an optimised multiplex real-time PCR method in order to diagnose bloodstream infections. MATERIAL AND METHODS In the present study, we evaluated the diagnostic performance of this optimised multiplex RT-PCR in blood samples collected from 110 septicaemia patients enrolled at the 108 Military Central Hospital, Hanoi, Vietnam. RESULTS Positive results were obtained by blood culture, the Light Cylcler-based SeptiFast® assay and our multiplex RT-PCR in 35 (32%), 31 (28%), and 31 (28%) samples, respectively. Combined use of the three methods confirmed 50 (45.5%) positive cases of bloodstream infection, a rate significantly higher compared to the exclusive use of one of the three methods (P=0.052, 0.012 and 0.012, respectively). The sensitivity, specificity and area under the curve (AUC) of our assay were higher compared to that of the SeptiFast® assay (77.4%, 86.1% and 0.8 vs. 67.7%, 82.3% and 0.73, respectively). Combined use of blood culture and multiplex RT-PCR assay showed a superior diagnostic performance, as the sensitivity, specificity, and AUC reached 83.3%, 100%, and 0.95, respectively. The concordance between blood culture and the multiplex RT-PCR assay was highest for Klebsiella pneumonia (100%), followed by Streptococcus spp. (77.8%), Escherichia coli (66.7%), Staphylococcus spp. (50%) and Salmonella spp. (50%). In addition, the use of the newly established multiplex RT-PCR assay increased the spectrum of identifiable agents (Acintobacter baumannii, 1/32; Proteus mirabilis, 1/32). CONCLUSION The combination of culture and the multiplex RT-PCR assay provided an excellent diagnostic accomplishment and significantly supported the identification of causative pathogens in clinical samples obtained from septic patients.

Scarification in sub-Saharan Africa: social skin, remedy and medical import

Various forms of body modification may be observed in sub‐Saharan Africa. Hypotheses and theories of scarification and tribal marking in sub‐Saharan Africa are described, plus the procedure of scarification, examples from several African countries, assumed effects in prevention and treatment of diseases, and the medical risks resulting from unsterile manipulation.