Role of Cytokines in Trypanosoma brucei-Induced Anaemia: A Review of the Literature

Background: Anaemia is an important complication of trypanosomiasis. The mechanisms through which trypanosomal infection leads to anaemia are poorly defined. A number of studies have implicated inflammatory cytokines, but these data are limited and inconsistent. In this article, we reviewed the published literature on cytokines associated with Trypanosoma brucei infections and their role in the immunopathology leading to anaemia.Methodology: Articles were searched in PubMed through screening of titles and abstracts with no limitation on date of publishing and study design. Articles in English were searched using keywords “African trypanosomiasis”, “sleeping sickness”, “Trypanosoma brucei”, in all possible combinations with “anaemia” and/or “cytokines”.Results: Twelve articles examining cytokines and their role in trypanosomeinduced anaemia were identified out of 1095 originally retrieved from PubMed. None of the articles identified were from human-based studies. A total of eight cytokines were implicated, with four cytokines (IFN-γ, IL-10, TNF-α, IL-12) showing an association with anaemia. These articles reported that mice lacking TNF-α were able to control anaemia, and that IFN-γ was linked to severe anaemia given its capacity to suppress erythropoiesis, while IL-10 was shown to regulate IFN-γ and TNF-α, providing a balance that was associated with severity of anaemia. IFN-γ and TNF-α have also been reported to work in concert with other factors such as nitric oxide and iron in order to induce anaemia.Conclusion: IFN-γ, IL-10, and TNF-α were the three major cytokines identified to beheavily involved in anaemia caused by Trypanosoma brucei infection. The anti-inflammatory cytokine, IL-10, was shown to counter the effects of proinflammatory cytokines in order to balance the severity of anaemia. The mechanism of anaemia is multifactorial and therefore requires further, more elaborate research. Data from human subjects would also shed more light

An outbreak of intestinal schistosomiasis, alongside increasing urogenital schistosomiasis prevalence, in primary school children on the shoreline of Lake Malawi, Mangochi District, Malawi

Background: Intestinal schistosomiasis was not considered endemic in Lake Malawi until 14 November 2017 when populations of Biomphalaria pfeifferi were first reported; in May 2018, emergence of intestinal schistosomiasis was confirmed. This emergence was in spite of ongoing control of urogenital schistosomiasis by preventive chemotherapy. Our current study sought to ascertain whether intestinal schistosomiasis is transitioning from emergence to outbreak, to judge if stepped-up control interventions are needed. Methods: During late-May 2019, three cross-sectional surveys of primary school children for schistosomiasis were conducted using a combination of rapid diagnostic tests, parasitological examinations and applied morbidity-markers; 1) schistosomiasis dynamics were assessed at Research Article IDOP Samama (n = 80) and Mchoka (n = 80) schools, where Schistosoma mansoni was first reported, 2) occurrence of S. mansoni was investigated at two non-sampled schools, Mangochi Orphan Education and Training (MOET) (n = 60) and Koche (n = 60) schools, where B. pfeifferi was nearby, and 3) rapid mapping of schistosomiasis, and B. pfeifferi, conducted across a further 8 shoreline schools (n = 240). After data collection, univariate analyses and Chi-square testing were performed, followed by binary logistic regression using generalized linear models, to investigate epidemiological associations. Results: In total, 520 children from 12 lakeshore primary schools were examined, mean prevalence of S. mansoni by ‘positive’ urine circulating cathodic antigen (CCA)-dipsticks was 31.5% (95% Confidence Interval (CI): 27.5–35.5). Upon comparisons of infection prevalence in May 2018, significant increases at Samama (Relative Risk (RR) = 1.7, 95% CI: 33 1.4–2.2) and Mchoka (RR = 2.7, 95% CI: 1.7–4.3) schools were observed. Intestinal schistosomiasis was confirmed at MOET (18.3%) and Koche (35.0%) schools, and in all rapid mapping schools, ranging from 10.0% to 56.7%. Several populations of B. pfeifferi were confirmed, with two new eastern shoreline locations noted. Mean prevalence of urogenital schistosomiasis was 24.0% (95% CI: 20.3–27.7). Conclusions: We notify that intestinal schistosomiasis, once considered non-endemic in Lake Malawi, is now transitioning from emergence to outbreak. Once control interventions can resume after coronavirus disease 2019 (COVID-19) suspensions, we recommend stepped-up preventive chemotherapy, with increased community-access to treatments, alongside renewed efforts in appropriate environmental control

An alien intermediate snail host in Malawi - Orientogalba viridis (Quoy and Gaimard, 1832) - A new concern for schistosomiasis transmission in Africa?

The freshwater amphibious snail Orientogalba viridis commonly occurs in eastern Asia, on certain Pacific islands and more importantly has recently dispersed into Europe. Since this snail is now considered an invasive species, its distribution is of growing parasitological interest as an alien intermediate host for various trematodes, particularly liver flukes. As part of ongoing surveillance for snail-borne diseases in Malawi, a population of O. viridis was first observed in May 2023, alongside an alarming presence of a human schistosome cercaria. This snail population later underwent detailed morphological characterisation with both snail and parasite identities confirmed upon DNA barcoding. This seminal observation triggered more extensive local snail surveys, finding 3 further populations in separated rice paddies, with further field-caught snails (n = 465) screened for infection and a selection used for repeated experimental challenges with miracidia from Schistosoma haematobium and Schistosoma mattheei. Although no field-caught (and experimentally exposed) snail was seen to shed schistosome cercariae, molecular xenomonitoring for schistosomiasis provided tangible evidence of putative transmission potential. Our first report of O. viridis here in Malawi, and more broadly in Africa, flags a need for increased vigilance for this invasive species alongside local clarification(s) of its transmission potential for trematodiases of either medical and/or veterinary importance

A first report of Pseudosuccinea columella (Say, 1817), an alien intermediate host for liver fluke, in Malawi

Starting in October 2021, quarterly malacological surveys have been undertaken in Malawi, with the sampling of 12 specified freshwater habitats throughout a calendar year. Each survey monitors the presence of aquatic intermediate snail hosts of medical and veterinary importance. In March 2023, the alien lymnaeid species Pseudosuccinea columella was encountered for the first time in the surveys, in Nsanje District. This species identity was later confirmed upon DNA analysis of mitochondrial ribosomal 16S sequences. In July 2023, P. columella was also noted at single sites within Mangochi and Chikwawa Districts, and again in Nsanje District, with an additional location observed. Of particular importance, our sampled location in Mangochi District was directly connected to Lake Malawi, which expands the species list of invasive molluscs in this lake. While P. columella is a well-known intermediate snail host for human and animal fascioliasis, screening collected snails for trematode cercariae, alongside molecular xenomonitoring, did not yield equivocal evidence of active fluke infection. However, the newly recognized presence of this alien intermediate snail host within Lake Malawi, and along the Shire River Valley, flags a new concern in altered local transmission potential for human and animal fascioliasis

Grey nails predict low CD4 cell count among untreated patients with HIV infection in Malawi

Background: Alternative criteria for initiating antiretroviral therapy to CD4 testing or clinical illness are needed in Malawi. Method: We tested if grey nails could be used to identify patients with a CD4 cell count less than 200 cells/mu l who had not yet presented with AIDS-defining illnesses. Results: Using a set of 242 photographs we showed good inter-observer agreement for grey nails (kappa = 0.66; P < 0.0001) and the positive predictive value of grey nails for a CD4 cell count of less than 200 cells/mu l was 81% (chi(2) < 0.0001). Conclusions: Grey nails have been associated with HIV infection and we have shown significant correlation of this sign with a low CD4 cell count. For clinicians working in sub-Saharan Africa without access to CD4 cell count testing, grey or DB nails represent an additional staging sign to help identify a sub-group of patients likely to benefit from ART. (c) 2006 Lippincott Williams & Wilkins

Lung fluid immunoglobulin from HIV-infected subjects has impaired opsonic function against pneumococci

Background. The incidence of pneumococcal pneumonia is greatly increased among human immunodeficiency virus (HIV)-infected subjects, compared with among non-HIV-infected subjects. Lung fluid levels of immunoglobulin G (IgG) specific for pneumococcal capsular polysaccharide are not reduced in HIV-infected subjects; therefore, we examined immunoglobulin subtypes and compared lung fluid IgG opsonic function in HIV-infected subjects with that in healthy subjects. Methods. Bronchoalveolar lavage (BAL) fluid and serum samples were collected from 23 HIV-infected and 26 uninfected subjects. None of the subjects were receiving highly active antiretroviral therapy, and none had received pneumococcal vaccination. Pneumococcal capsule-specific IgG levels in serum and BAL fluid were measured by enzyme-linked immunosorbent assay, and IgG was concentrated from 40 mL of BAL fluid. Opsonization and opsonophagocytosis of pneumococci with serum, BAL fluid, and BAL IgG were compared between HIV-infected subjects and healthy subjects. Results. The effect of type 1 pneumococcal capsular polysaccharide - specific IgG in opsonizing of pneumococci was significantly less using both serum and BAL IgG from HIV-infected subjects, compared with serum and BAL IgG from healthy subjects (mean level, 8.9 fluorescence units [95% confidence interval, 8.1-9.7 fluorescence units] vs. 12.1 fluorescence units [95% confidence interval, 9.7-15.2 fluorescence units]; P = .002 for lung BAL IgG). The opsonophagocytosis of pneumococci observed using BAL IgG from HIV-infected subjects was significantly less than that observed using BAL IgG from healthy subjects (37 fluorescence units per ng of IgG [95% confidence interval, 25-53 fluorescence units per ng of IgG] vs. 127 fluorescence units per ng of IgG [95% confidence interval, 109-145 fluorescence units per ng of IgG]; P < .001). Conclusion. HIV infection is associated with decreased antipneumococcal opsonic function in BAL fluid and serum