BACKGROUND: Drug interactions between antiretroviral drugs (ARVs) and anthelminthic drugs, ivermectin (IVM) and praziquantel (PZQ) were assessed by investigating their permeation through the Caco-2 cell monolayers in a transwell. The impact of anthelminthics on the transport of ARVs was determined by assessing the apical to basolateral (AP --> BL) [passive] and basolateral to apical (BL --> AP) [efflux] directions alone, and in presence of an anthelminthic. The reverse was conducted for the assessment of the influence of ARVs on anthelminthics. METHODS: Samples from the AP and BL compartments were taken at 60, 120, 180 and 240 min and quantified either by HPLC or radiolabeled assay using a liquid scintillating counter for the respective drugs. Transepithelial resistance (TEER) was used to assess the integrity of the monolayers. The amount of compound transported per second (apparent permeability, Papp) was calculated for both AP to BL (PappAtoB), and BL to AP (PappBtoA) movements. Samples collected after 60 min were used to determine the efflux ratio (ER), quotient of secretory permeability and absorptive permeability (PappBL-AP/PappAP-BL). The reverse, (PappAP-BL/PappBL-AP) constituted the uptake ratio. The impact of SQV, EFV and NVP on the transport of both IVM and PZQ were investigated. The effect of LPV on the transport of IVM was also determined. The influence of IVM on the transport of SQV, NVP, LPV and EFV; as well as the effect PZQ on the transport of SQV of was also investigated, and a two-tailed p value of <0.05 was considered significant. RESULTS: IVM significantly inhibited the efflux transport (BL --> AP movement) of LPV (ER; 6.7 vs. 0.8, p = 0.0038) and SQV (ER; 3.1 vs. 1.2 p = 0.00328); and increased the efflux transport of EFV (ER; 0.7 vs. 0.9, p = 0.031) suggesting the possibility of drug transporter mediated interactions between the two drugs. NVP increased the efflux transport of IVM (ER; 0.8 vs. 1.8, p = 0.0094). CONCLUSIONS: The study provides in vitro evidence of potential interactions between IVM, an anthelminthic drug with antiretroviral drugs; LPV, SQV, NVP and EFV. Further investigations should be conducted to investigate the possibility of in vivo interactions.

BACKGROUND: Neurosyphilis is the tertiary stage of Treponema pallidum infection that involves the central nervous system, which occurs within days or weeks after an initial syphilis infection, especially in immunocompromised patients. The diagnosis of neurosyphilis is quite challenging as it is uncommon and often presents with obscure symptoms since any organ system may be involved. CASE PRESENTATION: We describe a case of a 40-year-old African man who is human immunodeficiency virus positive with early neurosyphilis who presented with a stiff neck, headache, confusion, restlessness, and a left-sided chest pain; he did not respond to an empiric treatment of ceftriaxone and fluconazole for meningitis, and tramadol for headache. Ten days after admission, he developed generalized tonic-clonic convulsions; on examination he had ipsilateral facial nerve palsy and an oral ulcer, and responded well to benzathine penicillin treatment. CONCLUSIONS: Laboratory diagnosis of neurosyphilis is challenging because to date there is no single laboratory test which is considered sensitive enough for diagnosis of the disease, especially in resource-limited settings. Clinical judgment is still an important part of diagnosis; and neurosyphilis should be considered a diagnostic differential in patients with Human Immunodeficiency Virus presenting with central nervous system involvement and in other high-risk patients.

Oesophageal carcinoma (OC) is highly prevalent in Western Kenya especially among the members of the Kalenjin community who reside in the Northern and Southern areas of the Rift Valley. Previous authors have suggested potential association of environmental and genetic risk factors with this high prevalence. The environmental factors that have been suggested include contamination of food by mycotoxins and/or pesticides, consumption of traditional alcohol (locally referred to "Busaa" and "Chan'gaa"), use of fermented milk ("Mursik"), poor diet, tobacco use and genetic predisposition. The aim of this paper is to critically examine the potential contribution of each of the factors that have been postulated to be associated with the high prevalence of the disease in order to establish the most likely cause. We have done this by analyzing the trends, characteristics and behaviours that are specifically unique in the region, and corroborated this with the available literature. From our findings, the most plausible cause of the high incidence of OC among the Kalenjin community is mycotoxins, particularly fumonisins from the food chain resulting from poor handling of cereals; particularly maize combined with traditional alcohol laced with the toxins interacting synergistically with other high-risk factors such as dietary deficiencies associated alcoholism and viral infections, especially HPV. Urgent mitigating strategies should be developed in order to minimize the levels of mycotoxins in the food chain.

BACKGROUND: Although herbal medical products are still widely used in Kenya, many of the medicinal plants used by traditional medical practitioners (TMPs) have not been documented, despite several challenges that are now threatening the sustainability of the practice. OBJECTIVE: To document the medicinal plants and healing methods used by TMPs in a region of Kenya with several recognized herbalists for potential research. MATERIALS AND METHODS: Semi-structured interviews, group discussions, and direct observations were used to collect ethnopharmacological information. The participant's bio-data, clinical conditions treated, methods of treatment, medicinal plants used, methods of preparation and administration, and dosage forms were recorded. RESULTS: A total of 99 medicinal plants and 12 complementary preparations employed in the treatment of 64 medical conditions were identified. The most widely used plant was Rotala tenella which was used to treat nine medicinal conditions; seven each for Aloe tweediae and Dovyalis abyssinica; and six each for Basella alba and Euclea divinorum. The plants belonged to 55 families with Fabaceae family being the most frequently used (10), followed by Apocynaceae and Solanaceae, each with six species, respectively. We identified plants used to determine the sex of an unborn baby and those used to treat several conditions including anthrax and cerebral malaria and herbs used to detoxify meat from an animal that has died from anthrax. Of special interest was R. tenella which is used to prevent muscle injury. CONCLUSIONS: We have documented several plants with potential therapeutic effects. Further research may be conducted to determine their efficacy. SUMMARY: The medicinal plants used by traditional healers in a community which still practices herbal medicine in Kenya were documented. A total of 99 medicinal plants and 12 complementary preparations employed in the treatment of 64 medical conditions were identified. Further research may be carried out in order to determine their therapeutic efficacies. Abbreviations Used: F(ic): Informant consensus factor, N(ur): Number of use reports in each category, N(s): Number of reported species, TMPs: Traditional medical practitioners.

The use of the antiretroviral drug tenofovir has been associated with nephrotoxicity. However, the overall impact of this adverse effect has not comprehensively evaluated. Some researchers have reported that it is quite severe to warrant monitoring for renal toxicity, while others have concluded that the magnitude may not be that significant. We report two clinical cases seen in our renal clinic with high creatinine levels suggestive of nephrotoxicity who reverted back to normality upon withdrawal of tenofovir.

Background: An inventory of the medicinal plants used by herbalists to treat various ailments in Tindiret area of Nandi County, Kenya was conducted by a team comprising of medical researchers and botanists with a view to preserve indigenous ethnobotanical knowledge and potential research and development of new drugs. Materials and Methods: Data was collected from practicing herbalists through semi-structured interviews, group discussions and observations. The types of medical conditions treated, treatment methods as well as the plants used were recorded. Results and Conclusion: A total of 50 medicinal plants belonging to 28 families used for the treatment of 32 medical conditions were recorded. The disease conditions which were treated by the highest number of plants were abdominal/colic pains with 15 different plants recorded (13%), respiratory disorders 15(13%) and infertility14 (12%). The most widely used medicinal plants were Vernonia amygdalina 7(7%), Toddalia asiatica 6(6%), Aloe kedongensis 5(5%) and Zanthoxylum gilletii 5(5%); whereas the families with the highest number of plant usage were Fabaceae 8(14%), Lamiaceae 4(8%) and Solanaceae 4(8%) plants respectively. The study documents important ethno-medical knowledge on the plants used by herbalists in Tindiret sub-county.

Background: Praziquantel (PZQ) is an antihelminthic drug whose P-glycoprotein (P-gp) substrate specificity has not been conclusively characterized. We investigated its specificity by comparing its in vitro intracellular accumulation in CEM (parental), and CEMvbl cells which over express P-gp, a drug efflux transporter. Saquinavir (SQV), a known substrate of efflux transporters was used as control.Methods: A reversed phase liquid chromatography method was developed to simultaneously quantify PZQ and SQV in cell culture media involving involved a liquid - liquid extraction followed by ultra-high performance liquid chromatography using a Hypurity C18 column and ultraviolet detection set at a wavelength of 215 nm. The mobile phase consisted of ammonium formate, acetonitrile and methanol (57:38:5 v/v). Separation was facilitated via isocratic elution at a flow rate of 1.5 ml/min, with clozapine (CLZ) as internal standard. This was validated over the concentration range of 1.6 to 25.6 μM for all analytes. Intracellular accumulation of SQV in CEMvbl was significantly lower compared to that in CEM cells (0.1 ± 0.031 versus 0.52 ± 0.046, p = 0.03 [p <0.05]).Results: Accumulation of PZQ in both cell lines cells were similar (0.05 ± 0.005 versus 0.04 ± 0.009, p = 0.4) suggesting that it is not a substrate of P-gp in CEM cells. In presence tariquidar, a known inhibitor of P-gp, the intracellular accumulation of SQV in CEMvbl cells increased (0.52 ± 0.068 versus 0.61 ± 0.102, p = 0.34 in CEM cells and 0.09 ± 0.015 versus 0.56 ± 0.089, p = 0.029 [p < 0.05] in CEMvbl cells). PZQ did not significantly affect the accumulation of SQV in either CEM (0.52 ± 0.068 versus 0.54 ± 0.061, p = 0.77), or in CEMvbl cells (0.09 ± 0.015 versus 0.1 ± 0.031, p = 0.89) cells compared to tariquidar, implying that PZQ is not an inhibitor of P-gp in CEMvbl cells.

PURPOSE: More than 80% of women with breast cancer in Kenya present to medical care with established late-stage disease. We sought to understand why women might not participate in breast cancer screening when it is offered by comparing the views of a cohort of those who attended a screening special event with those of community controls who did not attend. METHODS: All residents living close to three health centers in western Kenya were invited to participate in screening. Participants (attendees) underwent clinical breast examination by trained physician oncologists. In addition, women who consented were interviewed by using a modified Breast Cancer Awareness Module questionnaire. Nonattendees were interviewed in their homes the following day. RESULTS: A total of 1,511 attendees (1,238 women and 273 men) and 467 nonattendee women participated in the study. Compared with nonattendees, the women attendees were older, more often employed, knew that breast cancer presented as a lump, and were more likely to have previously felt a lump in a breast. In addition, they were more likely to report previously participating in screening activities, were more likely to have performed breast self-examination, and were less concerned about wasting a doctor's time. Almost all those surveyed (attendees and nonattendees) expressed interest in future breast cancer screening opportunities. CONCLUSION: The women who volunteer for breast cancer screening in western Kenya are more aware of breast cancer than those who do not volunteer. Screening recruitment should seek to close these knowledge gaps to increase participation.

We report a case of a 62 year-old patient who developed Palmar-plantar erythrodysesthesia upon receiving four cycles of capacitabine-based chemotherapy. She was on post surgical adjuvant treatment for invasive well differentiated adenocarcinoma of the colon. The clinical and therapeutic aspects of this chemotherapeutic adverse effect are discussed.

BACKGROUND: Cough syrups are widely used in the developing world, but safety of their use in infants and children less than two years has not been well documented. Some syrups contain multiple combinations of such drugs as promethazine, diphenhydramine and ephedrine; which are individually now contraindicated in children less than two years. Despite this, the syrups are available as over the counter drugs and may be dispensed to mothers who are unaware of the potentially hazardous effects to their infants. A descriptive cross-sectional study was used to investigate suitability of cough syrups sold within Eldoret municipality for use in children less than two years of age based on their formulations and available literature. METHODS: Two semi-structured questionnaires were administered to pharmacy attendants and mothers attending sick child clinic at a referral hospital to establish whether cough syrups containing more than one active ingredient of compounds, now contraindicated in children are administered to infants, and awareness of potential serious adverse effects. Data from labeled contents of cough syrups from retail pharmacies was recorded and corroborated with information from literature to determine those deemed to contain the ingredients. The second questionnaire was administered to mothers with children less than two years to ascertain whether they had used the identified syrups. A total of 260 mothers and 55 pharmacy attendants were interviewed. RESULTS: There was widespread use of the syrups in children, including infants, with 192 (74%) of the respondents having used identified syrups and over 90% of these on children less than 2 years including those less than three months.146 (76%) mothers had administered the syrup at double the recommended dose. CONCLUSION: The regulatory authorities should make concerted efforts to discourage use of cough syrups containing ingredients that pose adverse events to infants, including campaigns to educate pharmacy workers and mothers.

INTRODUCTION: The benefits of the use of antibiotics in the mass treatment for active trachoma and other diseases have been documented, but the secondary effects arising from such a programme have not been fully elucidated. The purpose of this study was to investigate the potential secondary benefits arising from the use of azithromycin in mass treatment of active trachoma in an economically challenged Kenyan nomadic community. METHODS: Health information reports for January 2005 to December 2010 were reviewed to determine the annual trends of infectious diseases in the two districts, Narok and Transmara. The year 2007 was considered as the baseline for mass drug administration (MDA). Odds ratios (OR) were used to describe the association. RESULTS: The mass distribution coverage in Narok was 83% in 2008, 74% in 2009 and 63% in 2010. The odds for malaria (OR = 1.13; 95% CI 1.12-1.14), diarrhoeal diseases (OR = 1.04; 95% CI 1.01-1.06), urinary tract infections (UTIs) (OR = 1.21; 95% CI 1.17-1.26), intestinal worms (OR, 4.98; 95% CI 4.68-5.3), and respiratory diseases other than pneumonia (OR, 1.15; 95% CI 1.13-1.16) were higher after three rounds of mass treatment, indicating a better outcome. Before the intervention, there was a reducing trend in the odds for respiratory diseases. In Transmara (control), there was an increase in odds for malaria, respiratory infections, UTIs and intestinal worms. The odds for diarrhoeal diseases, skin diseases and pneumonia decreased throughout the study period. CONCLUSION: Mass distribution of azithromycin may have contributed to the decrease in the prevalence of the respiratory infections in Narok District.

BACKGROUND: The medicinal plants used by herbalists in Kenya have not been well documented, despite their widespread use. The threat of complete disappearance of the knowledge on herbal medicine from factors such as deforestation, lack of proper regulation, overexploitation and sociocultural issues warrants an urgent need to document the information. The purpose of the study was to document information on medicinal plants used by herbalists in Marakwet District towards the utilization of indigenous ethnobotanical knowledge for the advancement of biomedical research and development. METHODS: Semi- structured oral interviews were conducted with 112 practicing herbalists. The types of plants used were identified and the conditions treated recorded. RESULTS: Herbal practice is still common in the district, and 111 plants were identified to have medicinal or related uses. Different herbal preparations including fruits and healing vegetables are employed in the treatment of various medical conditions. Veterinary uses and pesticides were also recorded. CONCLUSION: The study provides comprehensive ethnobotanical information about herbal medicine and healing methods among the Marakwet community. The identification of the active ingredients of the plants used by the herbalists may provide some useful leads for the development of new drugs.

The use of herbal medicine is increasingly finding more relevance today, especially with the recognition that we are facing more challenges in the treatment of some medical conditions such as diabetes and cancer. To date, there are not many publications or records on the traditional herbal medicine use among the various Kenyan communities despite the widespread use. There is therefore an urgent need to document traditional medicines in Kenya for future reference and research.The main objective of this review is to examine the current state of traditional herbal medicine practise in Kenya, the challenges facing the sector and the possible solutions to streamline the practice and maximize on the benefits. The method adopted in this research involved the analysis of the available records on herbal medicine in Kenya from various sources including internet and the available books. This information was then compared with those in other countries with established systems in order to establish the existing inadequacies. The various efforts to document herbal medicine incorporate into mainstream healthcare and the legal framework was also reviewed.

BACKGROUND: Clinically significant drug-drug interactions (CSDIs) involving antiretrovirals are frequent and under-recognized in developed countries, but data are lacking for developing countries. METHODOLOGY AND PRINCIPAL FINDINGS: To investigate the prevalence of CSDIs between antiretrovirals and coadministered drugs, we surveyed prescriptions dispensed in a large HIV clinic in Kenya. Of 1040 consecutive patients screened, 996 were eligible for inclusion. CSDIs were defined as 'major' (capable of causing severe or permanent damage, contraindicated, avoid or not recommended by the manufacturer, or requiring dose modification) or 'moderate' (manufacturers advise caution, or close monitoring, or capable of causing clinical deterioration). A total of 334 patients (33.5%) were at risk for a CSDI, potentially lowering antiretroviral drug concentrations in 120 (12%) patients. Major interactions most frequently involved rifampicin (12.4%, mostly with efavirenz) and azoles (2.7%) whereas moderate interactions were frequently azoles (13%), steroids (11%), and antimalarials (3%). Multivariable analyses suggested that patients at risk for CSDIs had lower CD4 counts (P = 0.006) and baseline weight (P = 0.023) and WHO Stage 3 or 4 disease (P<=0.007). Risk for CSDIs was not associated with particular regimens, although only 116 (11.6%) patients were receiving WHO second line regimens. CONCLUSIONS: One in three patients receiving antiretrovirals in our programme were at risk of CSDIs. Strategies need to be urgently developed to avoid important drug interactions, to identify early markers of toxicity and to manage unavoidable interactions safely in order to reduce risk of harm, and to maximize the effectiveness of mass antiretroviral deployment in Africa.

Background: Studies in developed countries have shown that drug interactions (DI) involving antiretroviral therapy (ARV) are frequent and under-recognized. No similar work has been carried out in developing countries, where use of fixed dose combinations (FDCs) limits the scope for dose modification.Methods: Retrospective survey of a large database of HIV+ adults enrolled into Ampath programme. Details of age, gender, weight, ARVs and concomitant medications were recorded. DI were identified from http://www.hiv-druginteractions.org and classified as: major (potential to cause life-threatening illness or hospitalization, 'contra-indicated' or 'not recommended' in SPC, or requiring dose modification of either, or both drugs); moderate (recommendation to 'avoid' in SPC, or having a >50% effect on the AUC); minor (likelihood of interaction [actual or theoretical] or having an effect of 25–50% AUC).Summary of results: Data from 1,000 consecutive patients (363 male, 637 female, aged 13 – 68 years; mean body weight 61.3 kg), who were followed up for 1–21 months (median 9, total 8,594 patient-months of follow up) were included. 750 (75%) were on first-line ARV (d4T, 3TC, NVP) and the use of individual drugs was as follows: d4T 758(75.8%), 3TC 950(95%), ZDV 211(21.2%), NVP 613 (61.3%), EFV 264 (26.4%), and LPVr 55 (5.5%). All ARVs were prescribed at standard doses, regardless of whether a DI was present or not. Major interactions were identified in 187 patients (18.7%), predominantly involving rifampicin 104 (10.4%) and azoles 82 (8.2%). Moderate interactions were identified in 142 patients (14.2%), involving steroids 76 (7.6%), azoles 34 (3.4%) and antimalarials 27 (2.7%) patients. Minor interactions were recorded for 44 patients (4.4%). A total of 279 patients (27.9%) had either a major or moderate interaction, while no drug interactions were recorded in 698 patients (69.8%).Conclusion: Clinically significant DIs were common, affecting over 1/4 patients receiving ART in Kenya, yet are frequently not recognized. Although TB medications accounted for a significant proportion of DIs, we identified other important interactions involving ARVs and azoles, as well as antimalarials. Given the relative lack of laboratory monitoring and widespread use of FDCs, strategies need to be developed urgently to avoid important drug interactions, to identify early markers of toxicity, and to manage unavoidable interactions safely, in order to reduce risk of harm, and to maximize the effectiveness of mass ARV deployment in Africa.