David O. Olaleye

Transforming health professions’ education through in-country collaboration: examining the consortia among African medical schools catalyzed by the Medical Education Partnership Initiative

BackgroundAfrican medical schools have historically turned to northern partners for technical assistance and resources to strengthen their education and research programmes. In 2010, this paradigm shifted when the United States Government brought forward unprecedented resources to support African medical schools. The grant, entitled the Medical Education Partnership Initiative (MEPI) triggered a number of south-south collaborations between medical schools in Africa. This paper examines the goals of these partnerships and their impact on medical education and health workforce planning.MethodsSemi-structured interviews were conducted with the Principal Investigators of the first four MEPI programmes that formed an in-country consortium. These interviews were recorded, transcribed and coded to identify common themes.ResultsAll of the consortia have prioritized efforts to increase the quality of medical education, support new schools in-country and strengthen relations with government. These in-country partnerships have enabled schools to pool and mobilize limited resources creatively and generate locally-relevant curricula based on best-practices. The established schools are helping new schools by training faculty and using grant funds to purchase learning materials for their students. The consortia have strengthened the dialogue between academia and policy-makers enabling evidence-based health workforce planning. All of the partnerships are expected to last well beyond the MEPI grant as a result of local ownership and institutionalization of collaborative activities.ConclusionsThe consortia described in this paper demonstrate a paradigm shift in the relationship between medical schools in four African countries. While schools in Africa have historically worked in silos, competing for limited resources, MEPI funding that was leveraged to form in-country partnerships has created a culture of collaboration, overriding the history of competition. The positive impact on the quality and efficiency of health workforce training suggests that future funding for global health education should prioritize such south-south collaborations.

Respiratory syncytial virus infection: denominator-based studies in Indonesia, Mozambique, Nigeria and South Africa

OBJECTIVE To assess the burden of respiratory syncytial virus (RSV)-associated lower respiratory infections (LRI) in children in four developing countries. METHODS A WHO protocol for prospective population-based surveillance of acute respiratory infections in children aged less than 5 years was used at sites in Indonesia, Mozambique, Nigeria and South Africa. RSV antigen was identified by enzyme-linked immunosorbent assay performed on nasopharyngeal specimens from children meeting clinical case definitions. FINDINGS Among children aged < 5 years, the incidence of RSV-associated LRI per 1000 child-years was 34 in Indonesia and 94 in Nigeria. The incidence of RSV-associated severe LRI per 1000 child-years was 5 in Mozambique, 10 in Indonesia, and 9 in South Africa. At all study sites, the majority of RSV cases occurred in infants. CONCLUSION These studies demonstrate that RSV contributes to a substantial but quite variable burden of LRI in children aged < 5 years in four developing countries. The possible explanations for this variation include social factors, such as family size and patterns of seeking health care; the proportion of children infected by human immunodeficiency syndrome (HIV); and differences in clinical definitions used for obtaining samples. The age distribution of cases indicates the need for an RSV vaccine that can protect children early in life.

An outbreak of African Swine Fever in Nigeria: virus isolation and molecular characterization of the VP72 gene of a first isolate from West Africa.

The isolation of 98/ASF/NG, a strain of African Swine Fever Virus (ASFV) associated with a 1998 epizootic in Nigeria, is reported. This first isolate of the virus from West Africa was identified through a successful polymerase chain reaction (PCR) amplification and sequencing of a 280 base pair (bp) fragment of the Major Capsid Protein (VP72) gene. Further amplification and sequence analysis of a 1.9 kilobase pair (kbp) fragment encompassing the complete VP72 gene showed that the isolate has a 92.2%, 92.4%, and 97.2% homology with previously sequenced Ugandan, Dominican Republican and Spanish isolates respectively. Of the 50 nucleotide changes observed in this highly conserved gene, 45 were found to result in 40 amino acid changes clustered around the central region (position 426 to 516) of the VP 72 protein while changes at the remaining 5 positions were silent. These changes also led to the loss of two out of the seven potential N-glycosylation sites which are in this gene conserved among all isolates. The possible epizootiological implications of such mutations in a highly conserved gene of a DNA virus is discussed in relation to this outbreak.

Malaria Induces Anemia through CD8 + T Cell-Dependent Parasite Clearance and Erythrocyte Removal in the Spleen

ABSTRACT  Severe malarial anemia (SMA) in semi-immune individuals eliminates both infected and uninfected erythrocytes and is a frequent fatal complication. It is proportional not to circulating parasitemia but total parasite mass (sequestered) in the organs. Thus, immune responses that clear parasites in organs may trigger changes leading to anemia. Here, we use an outbred-rat model where increasing parasite removal in the spleen escalated uninfected-erythrocyte removal. Splenic parasite clearance was associated with activated CD8+ T cells, immunodepletion of which prevented parasite clearance. CD8+ T cell repletion and concomitant reduction of the parasite load was associated with exacerbated (40 to 60%) hemoglobin loss and changes in properties of uninfected erythrocytes. Together, these data suggest that CD8+ T cell-dependent parasite clearance causes erythrocyte removal in the spleen and thus anemia. In children infected with the human malaria parasite Plasmodium falciparum, elevation of parasite biomass (not the number of circulating parasites) increased the odds ratio for SMA by 3.5-fold (95% confidence intervals [CI95%], 1.8- to 7.5-fold). CD8+ T cell expansion/activation independently increased the odds ratio by 2.4-fold (CI95%, 1.0- to 5.7-fold). Concomitant increases in both conferred a 7-fold (CI95%, 1.9- to 27.4-fold)-greater risk for SMA. Together, these data suggest that CD8+-dependent parasite clearance may predispose individuals to uninfected-erythrocyte loss and SMA, thus informing severe disease diagnosis and strategies for vaccine development. IMPORTANCE Malaria is a major global health problem. Severe malaria anemia (SMA) is a complex disease associated with partial immunity. Rapid hemoglobin reductions of 20 to 50% are commonly observed and must be rescued by transfusion (which can carry a risk of HIV acquisition). The causes and risk factors of SMA remain poorly understood. Recent studies suggest that SMA is linked to parasite biomass sequestered in organs. This led us to investigate whether immune mechanisms that clear parasites in organs trigger anemia. In rats, erythropoiesis is largely restricted to the bone marrow, and critical aspects of the spleen expected to be important in anemia are similar to those in humans. Therefore, using a rat model, we show that severe anemia is caused through CD8+ T cell-dependent parasite clearance and erythrocyte removal in the spleen. CD8 activation may also be a new risk factor for SMA in African children. Malaria is a major global health problem. Severe malaria anemia (SMA) is a complex disease associated with partial immunity. Rapid hemoglobin reductions of 20 to 50% are commonly observed and must be rescued by transfusion (which can carry a risk of HIV acquisition). The causes and risk factors of SMA remain poorly understood. Recent studies suggest that SMA is linked to parasite biomass sequestered in organs. This led us to investigate whether immune mechanisms that clear parasites in organs trigger anemia. In rats, erythropoiesis is largely restricted to the bone marrow, and critical aspects of the spleen expected to be important in anemia are similar to those in humans. Therefore, using a rat model, we show that severe anemia is caused through CD8+ T cell-dependent parasite clearance and erythrocyte removal in the spleen. CD8 activation may also be a new risk factor for SMA in African children.

Impact of Asymptomatic Malaria on Some Hematological Parameters in the Iwo Community in Southwestern Nigeria

Objective: To determine the prevalence of asymptomatic malaria among prospective blood donors and its effect on some hematological parameters. Subjects and Methods: Six hundred sixty-eight seemingly healthy individuals (501 men and 167 women) ≧16 years of age and without clinical symptoms in Iwo, Southwestern Nigeria, were screened for this study. A sample of 5 ml of blood was drawn from each participant for examination of malaria parasites and a full blood count. Thick and thin Giemsa-stained blood smears were prepared for malaria parasite identification and quantification. Estimations of hematocrit, hemoglobin concentration, and platelet and leukocyte counts were made using an automated Coulter counter (STKS model). Results: Out of the 668 participants examined, 141 (21.1%) were positive for malarial parasitemia. The parasite rate was significantly higher in men (25.5%) than in women (7.8%) (χ2 = 23.29, p < 0.001) and it was significantly associated with age (χ2 = 33.69, p < 0.001). Parasitemic participants had significantly lower mean values of hematocrit, hemoglobin concentration, and total leukocyte and platelet counts compared to aparasitemic individuals (t = 3.5, p < 0.001; t = 2.0, p = 0.04; t = 4.4, p < 0.001, and t = 5.3, p < 0.001, respectively). A low platelet count (<150 × 109/l) was significantly associated with malarial infection (OR 4.0; 95% CI 2.6–6.1). A person with a platelet count <150 × 109/l was 4 times more likely to have asymptomatic malarial infection than one with a count ≧150 × 109/l. Conclusion: Asymptomatic malaria is prevalent among blood donors in the study area and is associated with thrombocytopenia.

Antibodies to Lassa virus Z protein and nucleoprotein co-occur in human sera from Lassa fever endemic regions

It is not known whether the small 11-kDa Z protein of Lassa virus is immunogenic during human Lassa virus infection. To obtain evidence for the existence of an antibody response and to test the suitability of these antibodies for serosurveys, sera from Lassa fever endemic regions (Guinea and Nigeria, n=75) were tested for co-reactivity to Z protein and nucleoprotein (NP). Sera from a non-endemic region (Uganda, n=50) served as a specificity control. Z protein and NP were expressed in Escherichia coli, affinity-purified, and used as antigen in Western blot. Indirect immunofluorescence (IIF) with Lassa virus-infected cells was performed for comparison. Due to high unspecific reactivity of the African sera, Western blot testing was performed with a 1:1,000 serum dilution. Under these conditions, none of the control sera but 12% of the sera from endemic regions co-reacted with both Z protein and NP. Reactivity to Z protein was significantly associated with NP reactivity (P<10–6). NP and Z protein-specific antibodies were co-detected in 33% of the IIF-positive sera and in 5% of the IIF-negative sera (P=0.001). These data provide evidence for appearance of antibodies to Z protein and NP following Lassa virus infection. A recombinant blot for detection of both antibody specificities seems to be specific but less sensitive than IIF.

Complete Genome Sequence of a Genotype XVII Newcastle Disease Virus, Isolated from an Apparently Healthy Domestic Duck in Nigeria

ABSTRACT The first complete genome sequence of a strain of Newcastle disease virus (NDV) of genotype XVII is described here. A velogenic strain (duck/Nigeria/903/KUDU-113/1992) was isolated from an apparently healthy free-roaming domestic duck sampled in Kuru, Nigeria, in 1992. Phylogenetic analysis of the fusion protein gene and complete genome classified the isolate as a member of NDV class II, genotype XVII.

A new affordable flow cytometry based method to measure HIV‐1 viral load

Most commercially available assays for diagnosis of HIV infection have shown shortcomings in the detection and quantification of rare genotypes of the virus. Most of the assays do not detect subtype O (outlier) and/or N (nonmajor, nonoutlier) or new circulating recombinant forms (CRFs), which are becoming more important in sub‐Saharan Africa. Furthermore, the commonly available tests require costly measuring devices and expensive test kits, which are not easily affordable for developing countries. This study was designed to explore solutions to the problem of viral load assays in developing countries. Two forward primers, digoxygenin (DIG) and dinitrophenol (DNP) labeled, and one biotin (BIO) labeled reverse primer were used to amplify both, the HIV‐1‐5′LTR (long terminal repeat) region and an internal standard sequence. The two polymerase chain reaction (PCR)‐products were captured by anti‐DIG and anti‐DNP antibody coated microparticles. Flow cytometric analyses were carried out after labeling with streptavidin‐R‐phycoerythrine. The primer system used recognized all HIV‐1 subtypes. A coamplified internal standard warranted the functionality of the PCR and allows reproducible viral load measurements. Two drawbacks of current viral load measurements are overcome by the flow cytometry based test described hereof. First, all known worldwide relevant HIV‐1 subtypes including subtypes O, N, and new CRFs are quantifiable with high sensitivity (50 to >1 × 106 copies per PCR). Second, the cost per test can be reduced to less than 12 US

An improved PCR method for detection of HIV-1 proviral DNA of a wide range of subtypes and recombinant forms circulating globally.

instead of the current 50–100 US

Clinical and Immunological Profile of Pediatric HIV Infection in Ibadan, Nigeria.

. Additionally, the test described in this report offers the possibility to perform complete monitoring program (CD4 T‐cell count, CD4% and viral load) for the first time, with the same device for HIV‐infected persons.