Acute Phase Response of Albumin and Haptoglobin in Experimental Infection of the Olive Baboon, Papio Anubis, with Schistosoma Mansoni

Following infection of baboons with Schistosoma mansoni cercariae, a rapid four-fold increase in mean  serum haptoglobin concentrations was observed. These concentrations dropped to near pre-infection levels  following curative treatment of the infected animals with praziquantel. On challenge of the animals with a  second cercarial dose, haptoglobin concentrations demonstrated a more gradual increase that did not attain  the heights of the initial infection. Albumin concentrations displayed an inversely disproportionate relationship  to those of haptoglobin and decreases were much less pronounced. Whereas albumin was not a  sensitive indicator of schistosomiasis mansoni, haptoglobin proved to be useful in detecting the acute infection  and in determining prognosis of the disease in the olive baboon.

In vitro antileishmanial activity and phytochemical analysis of Carissa edulis against Leishmania major

Background: However, there is need to carry out scientific studies in order to confirm the medicinal properties of many plants used traditionally. Carissa edulis Forskk. (Gentiales: Apocynaceae) used by local communities for the treatment of various diseases has showed antiviral, antibacterial and antiprotozoal properties although there are no studies demonstrating its antileishmanial activity. Objective: To investigate in vitro antileishmanial activity of extracts of Carissa edulis on promastigote and amastigote forms of Leishmania major. Methodology: Solvent extraction of the stem parts of C. edulis was performed using water, methanol, petroleum ether, dichloromethane and ethyl acetate. Minimum inhibitory concentration (MIC), anti-amastigote and nitric oxide production assays were carried out to demonstrate antileishmanial activity of C. edulis extracts against the two forms of L. major parasite species: promastigote and amastigote. The extracts were also screened for phytochemical constituents present. Cytotoxicity assay was then done to assess their safe use as herbal medicinal products. Results: The C. edulis petroleum ether extract showed the strongest antileishmanial activity against L. major promastigotes (MIC=625μg/ml) with the water, dichloromethane and ethyl acetate extracts recording the weakest activity (MIC=2500μg/ml). The successive methanol extract reduced the number L. major amastigotes by 88.29% compared to the negative control (RPMI). The water (13.37μM), petroleum ether (12.93μM) and successive methanol extracts (12.82μM) produced nitrite values lower than the standard drugs Pentostam® (14.35μM) and Amphotericin B (14.13μM). Discussion: All C. edulis extracts have potential antileishmanial activity against L. major. Preliminary phytochemical screening of these extracts showed presence of alkaloids, terpenoids, phenols, anthraquinones and saponins. These phytochemicals were previously reported to have antileishmanial activity. Therefore, the plant extracts could offer an opportunity to develop cheaper antileishmanial alternatives to the more expensive pentavalent antimonials. Key words: C. edulis, L. major, promastigote, amastigot

Attitudes Toward Menstrual Suppression Among Cyclic and Continuous Contraceptive Vaginal Ring Users in Kenya

Objective: Multipurpose prevention technologies (MPTs) are developmental dual-purpose options that would provide women with a contraceptive as well as a prevention modality aimed at sexually transmitted infections. The contraceptive vaginal ring (CVR) has many properties that makes it an ideal MPT candidate. The objective of this study is to understand women’s attitudes towards menstrual suppression, a potential side effect of using a CVR, and how to address these attitudes for MPT vaginal rings in development. Materials and methods: We analyzed data derived from a subset of cohort study participants (n=45) in Thika, Kenya between January 2016- December 2018. The primary study enrolled 121 women 18-40 years with bacterial vaginosis and randomized them to cyclic or continuous CVR use for eight months. During the 6-month follow-up, a questionnaire eliciting attitudes towards menstrual suppression was administered. Responses to the menstrual suppression questionnaire between participants in the cyclic and continuous CVR use groups were compared. Likert-scale responses were summed to create a menstrual suppression attitude summary score, and a hierarchical cluster analysis was conducted to identify similarities in response patterns among all participants. Results: Totally 81.8% of continuous CVR users believed that one was less likely to get pregnant after using hormonal medication to suppress menses, compared to 47.8% of cyclic CVR users (P=0.02), and were more worried it would cause long-term health effects (86.4% vs 60.9%, p = 0.05). The menstrual suppression attitude summary score ranged from 8 to 42, with lower scores indicating negative attitudes. The summary score identified three distinct clusters. When asked if menstrual suppression effects long-term health; 100% of Cluster 3 was worried compared to 80.8% of Cluster 2 and 46.2% of Cluster 1 (p = 0.03). The average summary score among Cluster 3 (Mean = 14.8, SD = 4.6) was lower (p < 0.001) and women were more worried about discomfort during sex (p=0.05) as well as their sexual partners feeling the ring (p=0.02). Conclusion: Women are more likely to have negative attitudes if they believe menstrual suppression hinders future reproductive health. Education on cycle control and fertility could mitigate negative attitudes and improve uptake of CVRs

Mechanisms controlling anaemia in Trypanosoma congolense infected mice.

Trypanosoma congolense are extracellular protozoan parasites of the blood stream of artiodactyls and are one of the main constraints on cattle production in Africa. In cattle, anaemia is the key feature of disease and persists after parasitaemia has declined to low or undetectable levels, but treatment to clear the parasites usually resolves the anaemia. The progress of anaemia after Trypanosoma congolense infection was followed in three mouse strains. Anaemia developed rapidly in all three strains until the peak of the first wave of parasitaemia. This was followed by a second phase, characterized by slower progress to severe anaemia in C57BL/6, by slow recovery in surviving A/J and a rapid recovery in BALB/c. There was no association between parasitaemia and severity of anaemia. Furthermore, functional T lymphocytes are not required for the induction of anaemia, since suppression of T cell activity with Cyclosporin A had neither an effect on the course of infection nor on anaemia. Expression of genes involved in erythropoiesis and iron metabolism was followed in spleen, liver and kidney tissues in the three strains of mice using microarrays. There was no evidence for a response to erythropoietin, consistent with anaemia of chronic disease, which is erythropoietin insensitive. However, the expression of transcription factors and genes involved in erythropoiesis and haemolysis did correlate with the expression of the inflammatory cytokines Il6 and Ifng. The innate immune response appears to be the major contributor to the inflammation associated with anaemia since suppression of T cells with CsA had no observable effect. Several transcription factors regulating haematopoiesis, Tal1, Gata1, Zfpm1 and Klf1 were expressed at consistently lower levels in C57BL/6 mice suggesting that these mice have a lower haematopoietic capacity and therefore less ability to recover from haemolysis induced anaemia after infection

Animal-related factors associated with moderate-to-severe diarrhea in children younger than five years in western Kenya: A matched case-control study

Background Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. Methodology/Principal findings We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children’s homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08–0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02–0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0–1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5–37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2–12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. Conclusions and significance Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents

Expanding contraceptive options for PMTCT clients: a mixed methods implementation study in Cape Town, South Africa

Abstract Background Clients of prevention of mother-to-child transmission (PMTCT) services in South Africa who use contraception following childbirth rely primarily on short-acting methods like condoms, pills, and injectables, even when they desire no future pregnancies. Evidence is needed on strategies for expanding contraceptive options for postpartum PMTCT clients to include long-acting and permanent methods. Methods We examined the process of expanding contraceptive options in five health centers in Cape Town providing services to HIV-positive women. Maternal/child health service providers received training and coaching to strengthen contraceptive counseling for postpartum women, including PMTCT clients. Training and supplies were introduced to strengthen intrauterine device (IUD) services, and referral mechanisms for female sterilization were reinforced. We conducted interviews with separate samples of postpartum PMTCT clients (265 pre-intervention and 266 post-intervention) to assess knowledge and behaviors regarding postpartum contraception. The process of implementing the intervention was evaluated through systematic documentation and interpretation using an intervention tracking tool. In-depth interviews with providers who participated in study-sponsored training were conducted to assess their attitudes toward and experiences with promoting voluntary contraceptive services to HIV-positive clients. Results Following the intervention, 6% of interviewed PMTCT clients had the desired knowledge about the IUD and 23% had the desired knowledge about female sterilization. At both pre- and post-intervention, 7% of clients were sterilized and IUD use was negligible; by comparison, 75% of clients used injectables. Intervention tracking and in-depth interviews with providers revealed intervention shortcomings and health system constraints explaining the failure to produce intended effects. Conclusions The intervention failed to improve PMTCT clients’ knowledge about the IUD and sterilization or to increase use of those methods. To address the family planning needs of postpartum PMTCT clients in a way that is consistent with their fertility desires, services must expand the range of contraceptive options to include long-acting and permanent methods. In turn, to ensure consistent access to high quality family planning services that are effectively linked to HIV services, attention must also be focused on resolving underlying health system constraints weakening health service delivery more generally

Regional Differences in Prevalence of HIV-1 Discordance in Africa and Enrollment of HIV-1 Discordant Couples into an HIV-1 Prevention Trial

Background: Most HIV-1 transmission in Africa occurs among HIV-1-discordant couples (one partner HIV-1 infected and one uninfected) who are unaware of their discordant HIV-1 serostatus. Given the high HIV-1 incidence among HIV-1 discordant couples and to assess efficacy of interventions for reducing HIV-1 transmission, HIV-1 discordant couples represent a critical target population for HIV-1 prevention interventions and prevention trials. Substantial regional differences exist in HIV-1 prevalence in Africa, but regional differences in HIV-1 discordance among African couples, has not previously been reported. Methodology/Principal Findings: The Partners in Prevention HSV-2/HIV-1 Transmission Trial (“Partners HSV-2 Study”), the first large HIV-1 prevention trial in Africa involving HIV-1 discordant couples, completed enrollment in May 2007. Partners HSV-2 Study recruitment data from 12 sites from East and Southern Africa were used to assess HIV-1 discordance among couples accessing couples HIV-1 counseling and testing, and to correlate with enrollment of HIV-1 discordant couples. HIV-1 discordance at Partners HSV-2 Study sites ranged from 8–31% of couples tested from the community. Across all study sites and, among all couples with one HIV-1 infected partner, almost half (49%) of couples were HIV-1 discordant. Site-specific monthly enrollment of HIV-1 discordant couples into the clinical trial was not directly associated with prevalence of HIV-1 discordance, but was modestly correlated with national HIV-1 counseling and testing rates and access to palliative care/basic health care (r = 0.74, p = 0.09). Conclusions/Significance: HIV-1 discordant couples are a critical target for HIV-1 prevention in Africa. In addition to community prevalence of HIV-1 discordance, national infrastructure for HIV-1 testing and healthcare delivery and effective community outreach strategies impact recruitment of HIV-1 discordant couples into HIV-1 prevention trials

Risk factors of visceral leishmaniasis: a case control study in north-western Ethiopia

Background Visceral leishmaniasis (VL, also called “kala-azar”), is a life threatening neglected tropical infectious disease which mainly affects the poorest of the poor. VL is prevalent in Ethiopia particularly in the northwest of the country. Understanding the risk factors of VL infection helps in its prevention and control. The aim of the present study was to identify the factors associated with VL. Methods A case–control study was carried out during the period of January-July 2013 in northwest Ethiopia. Cases and controls were diagnosed using clinical presentation, the rk39 rapid diagnostic test and Direct Agglutination Test (DAT). A total of 283 (84.8% males versus 15.2% females) participants were interviewed. 90 cases and 193 controls were involved, matched by age, sex and geographical location with a ratio of 1:2 (case: controls). Univariate and backward multivariate conditional logistic regression were used to identify risk factors of VL. Results Elevated odds of VL was associated with goat ownership (OR = 6.4; 95%: confidence interval [Cl]: 1.5-28.4), living in houses with cracked wall (OR = 6.4; 95% Cl: 1.6-25.6), increased family size (OR = 1.3; 95% Cl: 1.0-1.8) and the number of days spent in the farm field (OR = 1.1; 95% Cl: 1.0-1.2). However, daily individual activities around the home and farm fields, mainly sleeping on a bed (OR = 0.2; 95%: Cl 0.03-0.9), sleeping outside the house under a bed net (OR = 0.1; 95% Cl: 0.02-0.36)] and smoking plant parts in the house during the night time (OR = 0.1; 95% Cl: 0.01-0.6) were associated with decreased odds of being VL case. Conclusion Our findings showed that use of bed net and smoke could be helpful for the prevention of VL in the area particularly among individuals who spend most of their time in the farm. VL control effort could be focused on improving housing conditions, such as sealing cracks and crevices inside and outside houses. Further research is warranted to elucidate the role of goats in the transmission of L. donovani, assess the impact of bed nets and the role of the traditional practice of smoking plants

Tracking the Feeding Patterns of Tsetse Flies (Glossina Genus) by Analysis of Bloodmeals Using Mitochondrial Cytochromes Genes

Tsetse flies are notoriously difficult to observe in nature, particularly when populations densities are low. It is therefore difficult to observe them on their hosts in nature; hence their vertebrate species can very often only be determined indirectly by analysis of their gut contents. This knowledge is a critical component of the information on which control tactics can be developed. The objective of this study was to determine the sources of tsetse bloodmeals, hence investigate their feeding preferences. We used mitochondrial cytochrome c oxidase 1 (COI) and cytochrome b (cytb) gene sequences for identification of tsetse fly blood meals, in order to provide a foundation for rational decisions to guide control of trypanosomiasis, and their vectors. Glossina swynnertoni were sampled from Serengeti (Tanzania) and G. pallidipes from Kenya (Nguruman and Busia), and Uganda. Sequences were used to query public databases, and the percentage identities obtained used to identify hosts. An initial assay showed that the feeds were from single sources. Hosts identified from blood fed flies collected in Serengeti ecosystem, included buffaloes (25/40), giraffes (8/40), warthogs (3/40), elephants (3/40) and one spotted hyena. In Nguruman, where G. pallidipes flies were analyzed, the feeds were from elephants (6/13) and warthogs (5/13), while buffaloes and baboons accounted for one bloodmeal each. Only cattle blood was detected in flies caught in Busia and Uganda. Out of four flies tested in Mbita Point, Suba District in western Kenya, one had fed on cattle, the other three on the Nile monitor lizard. These results demonstrate that cattle will form an integral part of a control strategy for trypanosomiasis in Busia and Uganda, while different approaches are required for Serengeti and Nguruman ecosystems, where wildlife abound and are the major component of the tsetse fly food source

Antiretroviral Drugs Protect Against HIV-1 Infection in Heterosexuals

BackgroundAntiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.MethodsWe conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services.ResultsWe enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P&lt;0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P&lt;0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study.ConclusionsOral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.)