Breast cancer is the commonest cause of global cancer-related deaths in women and a public health burden in sub-Saharan Africa (SSA). Although the disease incidence in SSA seems lower, mortality rates are disproportionately high in comparison to high-income countries. The global disease burden is growing, with SSA reporting the majority of cases; however, the dearth of information results in insufficient data which is barely representative of the actual disease burden in this population. Future incidence predictions assign the subregion with a majority of the cases and associated deaths. Breast cancer presents with racial and ethnic variations, and available evidence suggests geographical diversity and persistent risk factors that have barely been explored in SSA. Breast cancer is a complex genetic disease, but the genetic risk factors in the extant African population, which is the most genetically diverse population, is scant and of low quality. This review focuses on the burden, prevalence, detection, treatment, survival, biology, as well as risk factors, and reinforces the need for breast cancer-associated risk factor investigation and population-specific studies in SSA.

Plasmodium falciparum is a highly lethal malaria parasite of humans. A major portion of its life cycle is dedicated to invading and multiplying inside erythrocytes. The molecular mechanisms of erythrocyte invasion are incompletely understood. P. falciparum depends heavily on sialic acid present on glycophorins to invade erythrocytes. However, a significant proportion of laboratory and field isolates are also able to invade erythrocytes in a sialic acid-independent manner. The identity of the erythrocyte sialic acid-independent receptor has been a mystery for decades. We report here that the complement receptor 1 (CR1) is a sialic acid-independent receptor for the invasion of erythrocytes by P. falciparum. We show that soluble CR1 (sCR1) as well as polyclonal and monoclonal antibodies against CR1 inhibit sialic acid-independent invasion in a variety of laboratory strains and wild isolates, and that merozoites interact directly with CR1 on the erythrocyte surface and with sCR1-coated microspheres. Also, the invasion of neuraminidase-treated erythrocytes correlates with the level of CR1 expression. Finally, both sialic acid-independent and dependent strains invade CR1 transgenic mouse erythrocytes preferentially over wild-type erythrocytes but invasion by the latter is more sensitive to neuraminidase. These results suggest that both sialic acid-dependent and independent strains interact with CR1 in the normal red cell during the invasion process. However, only sialic acid-independent strains can do so without the presence of glycophorin sialic acid. Our results close a longstanding and important gap in the understanding of the mechanism of erythrocyte invasion by P. falciparum that will eventually make possible the development of an effective blood stage vaccine. Plasmodium falciparum malaria is a blood parasite that lives for the most part inside red cells. It is responsible for the death of 1-2 million people every year. The mechanisms by which the parasite invades red cells are complex and not completely understood. For many years it has been known that proteins called glycophorins are used by the parasite to gain entry into the red cell. However, the existence of another protein that allows entry independent of glycophorins has been suspected for nearly as long. The identity of the alternative protein has been a mystery difficult to solve. In this article we present strong evidence that the alternative protein is the complement receptor 1. The complement receptor 1 is a well-studied protein that is known to be important in protecting red cells from attack by the host immune system as well as suspected of having other roles in the development of malaria complications. The recognition of the additional role of complement receptor 1 in red cell invasion will allow the definitive identification of malaria proteins that interact with it and that could be used in a future vaccine cocktail to block red cell invasion.

BackgroundRespiratory distress (RD), a symptom of underlying metabolic acidosis, has been identified as a major risk factor for mortality in children with severe malaria in Africa, yet the molecular mediators involved in the pathogenesis of RD have not been identified MethodsWe studied circulating levels of mediators of inflammation—including the cytokines tumor necrosis factor (TNF)–α and interleukin (IL)–10; the chemokines macrophage inflammatory protein (MIP)–1α, MIP-1β, and IL-8; and the immune activation marker neopterin—in children with RD, severe malarial anemia (SMA), cerebral malaria (CM), and uncomplicated malaria (UM) ResultsChildren with RD had significantly higher plasma levels of TNF-α, IL-10, and neopterin and a significantly higher TNF-α:IL-10 ratio than those without RD. In addition, the results demonstrated that, relative to UM, CM was associated with increased levels of TNF-α and decreased levels of MIP-1α, whereas SMA was associated with decreased levels of IL-10. Circulating levels of neopterin were inversely correlated with hemoglobin, whereas levels of MIP-1β were positively correlated with parasitemia ConclusionsWe conclude that distinct clinical presentations of severe malaria are associated with specific patterns of inflammatory mediators. In particular, we show, to our knowledge for the first time, that patients with malaria and RD have a strong and unbalanced proinflammatory response that may be involved in the pathogenesis of the underlying metabolic acidosis

Presumptive treatment of febrile illness patients for malaria remains the norm in endemic areas of West Africa, and "malaria" remains the top source of health facility outpatient visits in many West African nations. Many other febrile illnesses, including bacterial, viral, and fungal infections, share a similar symptomatology as malaria and are routinely misdiagnosed as such; yet growing evidence suggests that much of the burden of febrile illness is often not attributable to malaria. Dengue fever is one of several viral diseases with symptoms similar to malaria, and the combination of rapid globalization, the long-standing presence of Aedes mosquitoes, case reports from travelers, and recent seroprevalence surveys all implicate West Africa as an emerging front for dengue surveillance and control. This paper integrates recent vector ecology, public health, and clinical medicine literature about dengue in West Africa across community, regional, and global geographic scales. We present a holistic argument for greater attention to dengue fever surveillance in West Africa and renew the call for improving differential diagnosis of febrile illness patients in the region.

Chemokines regulate the host immune response to a variety of infectious pathogens. Since the role of chemokines in regulating host immunity in children with Plasmodium falciparum malaria has not previously been reported, circulating levels of β-chemokines (MIP-1α, MIP-1β, and RANTES) and their respective transcriptional profiles in ex vivo peripheral blood mononuclear cells (PBMCs) were investigated. Peripheral blood MIP-1α and MIP-1β levels were significantly elevated in mild and severe malaria, while RANTES levels decreased with increasing disease severity. β-Chemokine gene expression profiles in blood mononuclear cells closely matched those of circulating β-chemokines, illustrating that PBMCs are a primary source for the observed pattern of β-chemokine production during acute malaria. Statistical modeling revealed that none of the chemokines was significantly associated with either parasitemia or anemia. Additional investigations in healthy children with a known history of malaria showed that children with prior severe malaria had significantly lower baseline RANTES production than children with a history of mild malaria, suggesting inherent differences in the ability to produce RANTES in these two groups. Baseline MIP-1α and MIP-1β did not significantly differ between children with prior severe malaria and those with mild malaria. Additional in vitro experiments in PBMCs from healthy, malaria-naïve donors revealed that P. falciparum -derived hemozoin (Hz; malarial pigment) and synthetic Hz (β-hematin) promote a similar pattern of β-chemokine gene expression. Taken together, the results presented here demonstrate that children with severe malaria have a distinct profile of β-chemokines characterized by increased circulating levels of MIP-1α and MIP-1β and decreased RANTES. Altered patterns of circulating β-chemokines result, at least in part, from Hz-induced changes in β-chemokine gene expression in blood mononuclear cells.

The impact of malaria on global health has continually prompted the need to develop effective diagnostic strategies. In malaria endemic regions, routine diagnosis is hampered by technical and infrastructural challenges to laboratories. These laboratories lack standard facilities, expertise or diagnostic supplies; thus, therapy is administered based on clinical or self-diagnosis. There is the need for accurate diagnosis of malaria due to the continuous increase in the cost of medication, and the emergence and spread of drug resistant strains. However, the widely utilized Giemsa-stained microscopy and immunochromatographic tests for malaria are liable to several drawbacks, including inadequate sensitivity and false-positive outcomes. Alternative methods that offer improvements in performance are either expensive, have longer turnaround time or require a level of expertise that makes them unsuitable for point-of-care (POC) applications. These gaps necessitate exploration of more efficient detection techniques with the potential of POC applications, especially in resource-limited settings. This minireview discusses some of the recent trends and new approaches that are seeking to improve the clinical diagnosis of malaria.