Recognition of

Endotoxin from Gram-negative bacteria bound to CD14 signals through Toll-like receptor (TLR) 4, while components of Gram-positive bacteria, fungi, and Mycobacterium tuberculosis (M.tb.) preferentially use TLR2 signaling. We asked whether TLR4 plays any role in host resistance to M.tb. infection in vivo. Therefore, we infected the TLR4 mutant C3H/HeJ mice and their controls, C3H/HeN mice, with M.tb. by aerosol. TLR4 mutant mice had a reduced capacity to eliminate mycobacteria from the lungs, spread the infection to spleen and liver, with 10–100 times higher CFU organ levels than the wild-type mice and succumbed within 5–7 mo, whereas most of the wild-type mice controlled infection and survived the duration of the experiment. The lungs of TLR4 mutant mice showed chronic pneumonia with increased neutrophil infiltration, reduced macrophages recruitment, and abundant acid-fast bacilli. Furthermore, the pulmonary expression of TNF-α, IL-12p40, and monocyte chemoattractant protein 1 was significantly lower in C3H/HeJ mice when compared with the wild-type controls. C3H/HeJ-derived macrophages infected in vitro with M.tb. produced lower levels of TNF-α. Finally, the purified mycobacterial glycolipid, phosphatidylinositol mannosides, induced signaling in both a TLR2- and TLR4-dependent manner, thus suggesting that recognition of phosphatidylinositol mannosides in vivo may influence the development of protective immunity. In summary, macrophage recruitment and the proinflammatory response to M.tb. are impaired in TLR4 mutant mice, resulting in chronic infection with impaired elimination of mycobacteria. Therefore, TLR4 signaling is required to mount a protective response during chronic M.tb. infection.

The Onchocerca volvulus secretory protein Ov20/OvS1 represents a dominant antigen expressed in the infective larvae, microfilariae and adult stages of the parasite. The humoral responses to this protein have not yet been analysed in the polar clinical and immunological forms of onchocerciasis. Analysis by ELISA of class and subclass antibodies to Ov20/OvS1 in persons with the generalized or the hyperreactive form of onchocerciasis revealed similar strong responses of IgG1, IgG4 and IgM antibody levels in both forms of onchocerciasis and significant differences were observed in the IgE and IgA antibody classes. Computation of the ratios of antibodies showed that persons with the generalized form exhibited significantly higher ratios of IgG4 to IgG1, IgG4 to IgE, and IgM to IgE than patients with the hyperreactive form. To investigate the isotype recognition of antigenic sites on Ov20/OvS1 protein, three recombinantly expressed fragments (F1-3) of Ov20/OvS1 were probed using sera which strongly reacted with intact recombinant Ov20/OvS1. Epitope(s) on F1 comprising amino acid residues 1-63 were significantly recognized by IgG1 and IgE, while IgM recognized epitopes on all three fragments. The strongest reaction of IgM occurred with epitope(s) formed by residues 108-171 (F3). In contrast, IgG4 type antibodies were not reactive with either of the three OvS1 fragments, but they reacted with intact Ov20/OvS1 protein. Generalized onchocerciasis, unable to eliminate microfilariae, and hyperreactive onchocerciasis, with a high potency to eliminate or to reduce parasite loads, can be distinguished by a distinct pattern of isotype responses to Ov20/OvS1.

Background Uganda has been making progress towards universal HIV test and treat since 2013 and the 2016 test and treat policy was expanded from the 2013 guidelines. The expanded policy was rolled out in 2017 across the country. The treatment outcomes of this new policy have not yet been assessed at program level. The objective of this study was to determine the treatment outcome of the HIV test and treat policy in TASO Tororo Clinic, Eastern Uganda. Methodology This was a retrospective cohort study using secondary data. The study involved 580 clients who were newly diagnosed HIV positive in TASO Tororo clinic between June 2017 and May 2018, who were then followed up for ART initiation, retention in care, viral load monitoring and viral load suppression. The data was analyzed using Stat 14.0 version statistical software application. Results Of the 580 clients, 93.1%(540) were adults aged �20 years. The uptake of test and treat was at 92.4%(536) and 12 months retention was at 78.7% (422). The factors associated with retention in care were a) being counselled before ART initiation, AOR 2.41 (95%CI, 1.56-3.71), b) having a treatment supporter, AOR 1.57 (95%CI, 1.02-2.43) and having an opportunistic infection, AOR 2.99 (95%CI:1.21-7.41). The viral load coverage was 52.4% (221) and viral load suppression rate was 89.1% (197) of clients monitored. Age <20 years was the only identified factor associated with vial load non suppression, AOR 7.35 (95% CI = 2.23-24.24).

The dispersal range of the vector Simulium neavei Roubaud (Diptera: Simuliidae) was investigated in an onchocerciasis focus in Kabarole district, western Uganda, adjacent to the Itwara Forest Reserve, where the species breeds in phoretic association with the river crab Potamonautes aloysiisabaudiae (Nobili) (Decapoda: Potamonautidae). Biting rates were highest at the edge of the forest, but blood-seeking flies were collected up to a distance of about 4 km from the forest. Entomological data did not agree with the geographical distribution of onchocerciasis, which is hyperendemic in larger distances from the forest. The possible reasons are discussed.

No abstract

SummaryThe protein Ov20/OvS1 was used as antigen in ELISA and Western blot in order to differentiate onchocerciasis from African mansonelliasis and to characterize the hyperreactive form of Onchocerca volvulus infection (sowda). The specificity of the IgG4 Western blot was 98% for the differentiation between persons with onchocerciasis and Mansonella microfilariae (mf) carriers (125 persons with M. perstans and 92 with M. streptocerca), whereas the IgG4 ELISA showed a specificity of 81% in 137 M. perstans mf carriers and 85% in 94 M. streptocerca mf carriers. The sensitivity of Ov20/OvS1 in identifying onchocerciasis using the IgG4 ELISA was 75% for 103 O. volvulus mf carriers with the generalized and 89% for 44 patients with the sowda form of onchocerciasis. IgE antibodies against OvS1 were found in 95% of 39 patients with hyperreactive onchocerciasis but only in 15% of 47 persons with the generalized form. Thus, Ov20/-OvS1 appears a promising candidate antigen for the diagnosis of onchocerciasis and in particular for the detection of the sowda type of disease.keywords Ov20/OvS1 protein, onchocerciasis, mansonelliasis, sowda correspondence Dr N. Brattig,

Introduction: Corona virus disease (COVID-19) is one of the topmost global hindrances to human existence. Rural settings have been reported to be more vulnerable in some parts of the world. In Uganda, community leaders in rural villages are among the immediate personnel mandated to support compliance with preventive guidelines, and to identify and report/deliver COVID-19 cases to health units. We examined the potential risks of COVID-19 transmission, knowledge levels, perceptions and opinions of Village Council Leaders (VCLs) in selected districts in Eastern Uganda, to support the design of risk-based COVID-19 control measures in rural settings, to protect lives better. Methodology: A convenience sample of ten VLCs were purposively selected in three districts in Eastern Uganda. Pretested questionnaires and in-depth interviews were used to assess the knowledge levels, perceptions, and opinions of respondents about COVID-19. An observational survey was also conducted to examine the barriers to effective control of COVID-19, with reference to health guidelines set by the Ugandan government and the World Health Organization. Data was analyzed using HyperRESEARCH 2.8 software, and STATA version-15.0. Results: Eighty percent of VCLs reported that they were formally engaged in the fight against COVID-19, and the common means of engagement were; dissemination of COVID-19 information by word of mouth, regulation of public events, and monitoring of visitors that come from distant places. All clients reported having received some information about this pandemic, but there was generally low knowledge on some vital aspects: 70% of the respondents did not know the meaning of COVID-19; 100% were uninformed on these common symptoms; headache, sore throat, nausea, and loss of taste & smell; 10% did not know if willingness to conform to health guidelines may affect COVID-19 prevention, and they believed that domestic animals are viable vectors. Radio was the commonest source of COVID-19 information, but it was confounded by poor quality of radio-signals. Most respondents were of the view that in the communities they lead; inaccessibility to authentic health information, financial constraints, and belief that COVID-19 is a fallacy, were some of the leading obstacles to the fight against the pandemic. Low awareness and misconceptions on COVID-19 could be explained by; technological challenges, low literacy levels, and dissemination of wrong information about this pandemic. From the observational survey, the major factors which might intensify the risk of COVID-19 spread were: scarcity of requirements for hand hygiene, face protection, violation of health guidelines and directives, porous borders, terrain, and use of potentially polluted open water sources. Conclusion: Communities in Eastern Uganda are vulnerable to the drastic spread of COVID-19 due to challenges related to: low awareness, poor compliance with preventive guidelines, finances, technology, terrain, illiteracy, scarcity of protective wear and hygiene resources. Awareness creation, material aid, execution of preventive rules, and more research on COVID-19 are warranted.