Mortality in Sickle Cell Anemia in Africa: A Prospective Cohort Study in Tanzania

Background: The World Health Organization has declared Sickle Cell Anemia (SCA) a public health priority. There are 300,000 births/year, over 75% in Africa, with estimates suggesting that 6 million Africans will be living with SCA if average survival reaches half the African norm. Countries such as United States of America and United Kingdom have reduced SCA mortality from 3 to 0.13 per 100 person years of observation (PYO), with interventions such as newborn screening, prevention of infections and comprehensive care, but implementation of interventions in African countries has been hindered by lack of locally appropriate information. The objective of this study was to determine the incidence and factors associated with death from SCA in Dar-es-Salaam.Methods and Findings: A hospital-based cohort study was conducted, with prospective surveillance of 1,725 SCA patients recruited from 2004 to 2009, with 209 (12%) lost to follow up, while 86 died. The mortality rate was 1.9 (95% CI 1.5, 2.9) per 100 PYO, highest under 5-years old [7.3 (4.8-11.0)], adjusting for dates of birth and study enrollment. Independent risk factors, at enrollment to the cohort, predicting death were low hemoglobin (= 102 mu mol/L) [1.7 (1.0-2.9); p = 0.044] as determined by logistic regression.Conclusions: Mortality in SCA in Africa is high, with the most vulnerable period being under 5-years old. This is most likely an underestimate, as this was a hospital cohort and may not have captured SCA individuals with severe disease who died in early childhood, those with mild disease who are undiagnosed or do not utilize services at health facilities. Prompt and effective treatment for anemia in SCA is recommended as it is likely to improve survival. Further research is required to determine the etiology, pathophysiology and the most appropriate strategies for management of anemia in SCA

IKKβ acts as a tumor suppressor in cancer-associated fibroblasts during intestinal tumorigenesis

Cancer-associated fibroblasts (CAFs) comprise one of the most important cell types in the tumor microenvironment. A proinflammatory NF-κB gene signature in CAFs has been suggested to promote tumorigenesis in models of pancreatic and mammary skin cancer. Using an autochthonous model of colitis-associated cancer (CAC) and sporadic cancer, we now provide evidence for a tumor-suppressive function of IKKβ/NF-κB in CAFs. Fibroblast-restricted deletion of Ikkβ stimulates intestinal epithelial cell proliferation, suppresses tumor cell death, enhances accumulation of CD4+Foxp3+ regulatory T cells, and induces angiogenesis, ultimately promoting colonic tumor growth. In Ikkβ-deficient fibroblasts, transcription of negative regulators of TGFβ signaling, including Smad7 and Smurf1, is impaired, causing up-regulation of a TGFβ gene signature and elevated hepatocyte growth factor (HGF) secretion. Overexpression of Smad7 in Ikkβ-deficient fibroblasts prevents HGF secretion, and pharmacological inhibition of Met during the CAC model confirms that enhanced tumor promotion is dependent on HGF–Met signaling in mucosa of Ikkβ-mutant animals. Collectively, these results highlight an unexpected tumor suppressive function of IKKβ/NF-κB in CAFs linked to HGF release and raise potential concerns about the use of IKK inhibitors in colorectal cancer patients

Yield loss due to the stemborer Chilo partellus (Swinhoe) (Lepidoptera: Crambidae) at different nitrogen application rates to maize

International Journal of entomology, 2006; 42(3-4):487-494Field trials were conducted at Kibaha and Morogoro in eastern Tanzania during two seasons to evaluate the effect of nitrogen fertilization (0, 50, 75, 100 kg [N]/ha) on pest abundance, plant damage and yield loss of maize due to stemborers. In general, ear and grain weights increased linearly with nitrogen level. In the infested plot, grain weight increased 2.5 and 1.8 fold from 0 to 100 kg [N]/ha in the short and long rainy season, respectively, at Kibaha, and 1.4 and 1.6 times at Morogoro. Yield loss decreased with an increase in nitrogen application and the effect was stronger under high than low borer infestation levels. The results show the benefi cial effect of nitrogen on the plant’s ability to compensate for borer damage. Analysis of economic benefi ts of applying fertilizer and insecticide treatment indicated that using insecticides is not profi table under high-pest-low-soil fertility conditions

Yield loss due to the stemborer Chilo partellus (Swinhoe) (Lepidoptera: Crambidae) at different nitrogen application rates to maize

International Journal of entomology, 2006; 42(3-4):487-494Field trials were conducted at Kibaha and Morogoro in eastern Tanzania during two seasons to evaluate the effect of nitrogen fertilization (0, 50, 75, 100 kg [N]/ha) on pest abundance, plant damage and yield loss of maize due to stemborers. In general, ear and grain weights increased linearly with nitrogen level. In the infested plot, grain weight increased 2.5 and 1.8 fold from 0 to 100 kg [N]/ha in the short and long rainy season, respectively, at Kibaha, and 1.4 and 1.6 times at Morogoro. Yield loss decreased with an increase in nitrogen application and the effect was stronger under high than low borer infestation levels. The results show the benefi cial effect of nitrogen on the plant’s ability to compensate for borer damage. Analysis of economic benefi ts of applying fertilizer and insecticide treatment indicated that using insecticides is not profi table under high-pest-low-soil fertility conditions

Educating enough competent health professionals: advancing educational innovation at Muhimbili University of Health and Allied Sciences, Tanzania.

Sarah MacFarlane and colleagues share their lessons engaging in educational reform and faculty development with the Muhimbili University of Health and Allied Sciences in Tanzania and the University of California San Francisco

Report from the first Tanzania Liver Cancer Conference: a call for action to unite in the fight against liver cancer in Sub-Saharan Africa, 17-18 March 2023, Dar es Salaam, Tanzania.

The first Tanzania Liver Cancer Conference (TLCC2023) took place on 17-18 March 2023 in Dar es Salaam, Tanzania with the aim of raising awareness among healthcare providers on the problem that liver cancer poses to the Tanzanian population and the urgent need to address this important issue. The conference focused on the following agenda items: 1) to build awareness among local healthcare providers on the status of liver cancer in Tanzania and the available diagnostic and management options, 2) to update Tanzanian healthcare providers on the current standard of care for liver cancer provided in developed countries and recent advancements in liver cancer care and 3) to promote an inclusive and multidisciplinary approach in research and the clinical care of patients with liver cancer in Tanzania. TLCC2023 was preceded by community-facing pre-conference activities, including screening 684 community members for hepatitis B virus free of charge. The conference was attended by 161 healthcare professionals from varying disciplines across Tanzania and abroad. TLCC2023 featured over 30 speakers from Tanzania, Kenya, Egypt, India and the United States that comprehensively covered a wide range of topics related to research and clinical care of liver cancer patients. A holistic and unified approach integrating both private and public sectors is vital in improving care for patients with liver cancer, and this was a common theme ingrained in the majority of presentations. Overall, the conference was well-received by attendees and knowledge assessment scores improved from 50% pre-conference to 75% post-conference (p < 0.001), demonstrating its educational value. As Tanzania's first conference on the subject, TLCC2023 marked an important milestone in a united fight against liver cancer in the country and beyond

Universities graduating health professionals in Tanzania.

<p>Source: authors (EEK, EL, and CM).</p

IKKα promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells

The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα) as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ)-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC) therapy

IKKalpha promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells.

The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IkappaB kinase alpha (IKKalpha) as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKalpha kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon gamma (IFNgamma)-expressing M1-like myeloid cells. In IKKalpha mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKalpha mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKalpha as a promising target for colorectal cancer (CRC) therapy