Combined chemotherapy manifest less severe immunopathology effects in helminth-protozoa comorbidity.

BACKGROUND: Co-infection with Leishmania major and Schistosoma mansoni may have significant consequences for disease progression, severity and subsequent transmission dynamics. Pentavalent antimonials and Praziquantel (PZQ) are used as first line of treatment for Leishmania and Schistosoma infections respectively. However, there is limited insight on how combined therapy with the standard drugs impacts the host in comorbidity. The study aimed to determine the efficacy of combined chemotherapy using Pentostam (P) and PZQ in murine model co-infected with L. major and S. mansoni. METHODS: A 3 × 4 factorial design with three parasite infection groups (Lm, Sm, Lm + Sm to represent L. major, S. mansoni and L. major + S. mansoni respectively) and four treatment regimens [P, PZQ, P + PZQ, and PBS designating Pentostam (GlaxoSmithKline UK), Praziquantel (Biltricide®, Bayer Ag. Leverkusen, Germany), Pentostam + Praziquantel and Phosphate buffered saline] as factors was applied. RESULTS: Significant changes were observed in the serum Interferon gamma (IFN-γ), and Macrophage inflammatory protein-one alpha (MIP-1α) levels among various treatment groups between week 8 and week 10 (p < 0.05). There was increased IFN-γ in the L. major infected mice subjected to PZQ and PBS, and in L. major + S. mansoni infected BALB/c mice treated with P + PZQ. Subsequently, MIP-1α levels increased significantly in both the L. major infected mice under PZQ and PBS and in L. major + S. mansoni infected BALB/c mice undergoing concurrent chemotherapy with P + PZQ between 8 and 10 weeks (p < 0.05). In the comorbidity, simultaneous chemotherapy resulted in less severe histopathological effects in the liver. CONCLUSION: It was evident, combined first line of treatment is a more effective strategy in managing co-infection of L. major and S. mansoni. The findings denote simultaneous chemotherapy compliments immunomodulation in the helminth-protozoa comorbidity hence, less severe pathological effects following the parasites infection. Recent cases of increased incidences of polyparasitism in vertebrates call for better ways to manage co-infections. The findings presented necessitate intrinsic biological interest on examining optimal combined chemotherapeutic agents strategies in helminth-protozoa concomitance and the related infections abatement trends vis-a-vis host-parasite relationships.

Determinants of breast cancer early detection for cues to expanded control and care: the lived experiences among women from Western Kenya.

BACKGROUND: Estimately, 70-80% of cancer cases are diagnosed in late stages in Kenya with breast cancer being a common cause of mortality among women where late diagnosis is the major ubiquitous concern. Numerous studies have focused on epidemiological and health policy dynamics essentially underestimating the determining factors that shape people's choices and cues to health care service uptake. The study sought to evaluate the knowledge, attitude and health seeking behavior towards breast cancer and its screening in a quest to explain why women present for prognosis and treatment when symptomatic pointers are in advanced stages, impeding primary prevention strategies. METHODS: Eight focus groups (6-10 members per group) and four key informant interviews were conducted among adult participants from rural and urban settings. Sessions were audio-recorded and transcribed. A thematic analysis of the data was based on the concepts of the health belief model. Data analysis was conducted using NVIVO10. RESULTS: Most women perceived breast cancer as a fatal disease and conveyed fear of having early screening. Rural women preferred self-prescribed medications and the use of alternative medicine for long periods before presenting for professional care on suspicion that the lump is cancerous. Accessibility to equipped health facilities, lack of information to establish effective follow-up treatment and low-income status were underscored as their major health seeking behavior barriers whereas, urban women identified marital status as their main barrier. Key informant interviews revealed that health communication programs emphasized more on communicable diseases. This could in part explain why there is a high rate of misconception and suspicion about breast cancer among rural and urban women in the study setting. CONCLUSIONS: Creating breast cancer awareness alongside clear guidelines on accessing screening and treatment infrastructure is critical. It was evident, a diagnosis of breast cancer or lump brings unexpected confrontation with mortality; fear, pain, cultural barriers, emotional and financial distress. Without clear referral channels to enable those with suspicious lumps or early stage disease to get prompt diagnosis and treatment, then well-meaning awareness will not necessarily contribute to reducing morbidity and mortality.

Symptomatic malaria diagnosis overestimate malaria prevalence, but underestimate anaemia burdens in children: results of a follow up study in Kenya.

BACKGROUND: The commonly accepted gold standard diagnostic method for detecting malaria is a microscopic reading of Giemsa-stained blood films. However, symptomatic diagnosis remains the basis of therapeutic care for the majority of febrile patients in malaria endemic areas. This study aims to compare the discrepancy in malaria and anaemia burdens between symptomatic diagnosed patients with those diagnosed through the laboratory. METHODS: Data were collected from Western Kenya during a follow-up study of 887 children with suspected cases of malaria visiting the health facilities. In the laboratory, blood samples were analysed for malaria parasite and haemoglobin levels. Differences in malaria prevalence between symptomatic diagnosis and laboratory diagnosis were analysed by Chi-square test. Bayesian probabilities were used for the approximation of the malaria and anaemia burdens. Regression analysis was applied to: (1) determine the relationships between haemoglobin levels, and malaria parasite density and (2) relate the prevalence of anaemia and the prevalence of malaria. RESULTS: The prevalence of malaria and anaemia ranged from 10% to 34%, being highest during the rainy seasons. The predominant malaria parasite was P. falciparum (92.3%), which occurred in higher density in children aged 2‒5 years. Fever, high temperature, sweating, shivering, vomiting and severe headache symptoms were associated with malaria during presumptive diagnosis. After conducting laboratory diagnosis, lower malaria prevalence was reported among the presumptively diagnosed patients. Surprisingly, there were no attempts to detect anaemia in the same cohort. There was a significant negative correlation between Hb levels and parasite density. We also found a positive correlation between the prevalence of anaemia and the prevalence of malaria after laboratory diagnosis indicating possible co-occurrence of malaria and anaemia. CONCLUSION: Symptomatic diagnosis of malaria overestimates malaria prevalence, but underestimates the anaemia burden in children. Good clinical practice dictates that a laboratory should confirm the presence of parasites for all suspected cases of malaria.

Pellagra in isoniazid preventive and antiretroviral therapy.

Pellagra is caused by cellular deficiency of niacin or its precursor amino acid, tryptophan. Isoniazid preventive therapy (IPT) is the administration of isoniazid (INH) to latent tuberculosis (TB) infection affected people preventing advancement to active TB disease. Although potentially life-saving for human immunodeficiency virus (HIV)-infected people with no active TB, IPT is arguably a possible player in pellagra in addition to well-known malnourishment determinants particularly in developing nations where diagnosis is often overlooked or delayed. A case study examines clinical presentation and possible causes of pellagra, in HIV + patient on isoniazid prophylaxis. The 30 year old female on routine antiretroviral therapy presented with diarrhea, abdominal discomfort, painful swallowing, and epigastric pain, facial rash spread on the forehead, nose, cheeks and the chin, upper and lower limbs. Withdrawal of isoniazid, administration of nicotinamide and niacin supplements showed clinical improvement in four weeks. Decreased serum tryptophan in persons living with HIV (PLHIV) under IPT and lack of minimum dietary proteins threshold would be pointers to isoniazid induced pellagra risk. Appropriate dietary intake and counseling ought to be emphasized among PLHIV. Tryptophan and nicotinamide serum levels should be part of baseline investigations in PLHIV starting IPT and where feasible clinically, niacin/nicotinamide supplementation be adopted.

Experimental therapeutic assays of Tephrosia vogelii against Leishmania major infection in murine model: in vitro and in vivo.

BACKGROUND: Conventional targeted leishmanicidal chemotherapy has persistently remained prohibitive for most economically deprived communities due to costs, associated time to accessing health services and duration for successful treatment programme. Alternatives are bound to be incorporated in rational management of leishmaniasis by choice or default due to accessibility and cultural beliefs. Therefore, there is need to rigorously investigate and appraise the activity of medicinal compounds that may have anti-leishmanicidal activity especially in the context of products that are already being utilized by the populations for other ailments but have limited information on their therapeutic value and possible cytoxicity. Hence, the study examined both in vivo and in vitro response of L. major infection to Tephrosia vogelii extracts in BALB/c mice as the mouse model. METHODS: A comparative study design was applied for the in vivo and in vitro assays of the extract with Pentostam (GlaxoSmithKline, UK) and Amphotericin B [Fungizone™, X-Gen Pharmaceuticals (US)] as standard drugs. RESULTS: In BALB/c mice where the chemotherapeutic extract was administered intraperitoneally, there was significantly (p < 0.05) larger reduction in lesion size and optimal control of parasite burden than those treated orally. However, standard drugs showed better activity. Tephrosia vogelii had 50% inhibitory concentration (IC50) and IC90 of 12 and 68.5 µg/ml respectively, while the standard drugs had IC50 and IC90 of 5.5 and 18 µg/ml for Pentostam and 7.8 and 25.5 µg/ml for Amphotericin B in that order. In the amastigote assay, the infection rates decreased with increase in chemotherapeutic concentration. The multiplication indices for L. major amastigotes in macrophages treated with 200 µg/ml of the standard drugs and extract were significantly different (p < 0.05). 200 µg/ml of T. vogelii extract showed a multiplication index of 20.57, 5.65% for Amphotericin B and 9.56% for Pentostam. There was also significant difference (p < 0.05) in levels of Nitric oxide produced in the macrophages. CONCLUSIONS: The findings demonstrated that T. vogelii extract has anti-leishmanial activity and further assays should be done to ascertain the active compounds responsible for anti-leishmanial activity.

Evaluation of leishmanicidal activity and cytotoxicity of Ricinus communis and Azadirachta indica extracts from western Kenya: in vitro and in vivo assays.

BACKGROUND: Despite advances to targeted leishmanicidal chemotherapy, defies around severe toxicity, recent emergence of resistant variants and absence of rational vaccine still persist. This necessitates search and/or progressive validation of accessible medicinal remedies including plant based. The study examined both in vivo and in vitro response of L. major infection to combined therapy of Ricinus communis and Azadirachta indica extracts in BALB/c mice as the mouse model. A comparative study design was applied. RESULTS: BALB/c mice, treated with combination therapy resulted in significantly (p < 0.05) larger reduction of lesion than those treated with monotherapies. The spleno-somatic index was found to be significantly low with combination therapy than monotherapies. Antiparasitic effect of A. indica and R. communis on amastigote with a 50 % inhibitory concentration (IC50) was of 11.5 and 16.5 µg mL(-1) respectively while combination therapy gave 9.0 µg ml(-1) compared to the standard drugs, Pentostam and amphotericin B which had an IC50 of 6.5 and 4.5 µg ml(-1) respectively. Optimal efficacy of A. indica and R. communis was 72 and 59.5 % respectively, combination therapy gave 88 %, while Pentostam and amphotericin B had 98 and 92 % respectively against amastigotes. Against promastigotes A. indica and R. Communis gave an IC50 of 10.1, 25.5 µg mL(-1) respectively, while combination, 12.2 µg mL(-1) against 4.1 and 5.0 µg ml(-1) for Pentostam and amphotericin B respectively. The optimal efficacy of the compounds against promastigotes was 78.0, 61.5 and 91.2 % (A. indica, R. communis and A. indica + R. communis respectively) against 96.5 and 98 % for Pentostam and amphotericin B respectively. The concentrations at optimal efficacy were significantly different (p < 0.05) among the test compounds. An evaluation of the IC50 values of the combination therapies clearly reveals synergistic effects. CONCLUSION: Combination therapy of A. indica and R. communis had best antileishmanial activity than the monotherapies. The active ingredients of both R. communis and A. indica need to be fractionated, and studied further for activity against Leishmania parasites.

Effectiveness of option B highly active antiretroviral therapy (HAART) prevention of mother-to-child transmission (PMTCT) in pregnant HIV women.

BACKGROUND: Ensuring that no baby is born with HIV is an essential step towards achieving an AIDS-free generation. To achieve this, strategies that decouple links between childbirth and HIV transmission are necessary. Traditional forms of prevention of mother-to-child transmission of HIV (PMTCT), has been recommended. Recognizing the importance and challenges of combination of methods to achieve rapid PMTCT, the World Health Organization (WHO) recommended option B Highly Active Antiretroviral Therapy (HAART) for all HIV-positive pregnant women. This study aimed to evaluate the effectiveness of the HAART in PMTCT. A cohort of HIV-infected pregnant women in Kenya were obtained from the DREAM Center, Nairobi. The study participants underwent adherence counselling and Option B of HAART [Nevirapine(NVP) + Lamivudine + Zidovudine] at the fourth week of gestation followed by an intravenous NVP administration intrapartum and postpartum NVP syrup to the respective infants for six weeks. Absolute pre-HAART and post-HAART CD4 counts and viral loads counts were determined. Comparison of the CD4 counts and viral loads before and after administration of HAART were done using Wilcoxon's Matched Pairs Signed-Ranks Test. FINDINGS: The mean absolute CD4 cell counts in mothers after administration of HAART was significantly higher (Z = 15.664, p < 0.001) than before the administration of HAART). Also the viral load of the mothers significantly (Z = 11.324, p < 0.001) reduced following HAART treatment. Following the HAART administration in mothers, up to 90% of children were confirmed to be HIV negative. CONCLUSION: Administration of HAART to mothers and children demonstrated an effective mechanism of PMTCT. However, other aspects of HAART such as adherence, costs, mothers behaviour during HAART, and the child feeding programme during the therapy should further be evaluated and ascertained how they can affect the overall efficacy of option B HAART in PMTCT.