HIV infection drives IgM and IgG3 subclass bias in Plasmodium falciparum-specific and total immunoglobulin concentration in Western Kenya.

BACKGROUND: HIV infection is associated with more frequent and severe episodes of malaria and may be the result of altered malaria-specific B cell responses. However, it is poorly understood how HIV and the associated lymphopenia and immune activation affect malaria-specific antibody responses. METHODS: HIV infected and uninfected adults were recruited from Bondo subcounty hospital in Western Kenya at the time of HIV testing (antiretroviral and co-trimoxazole prophylaxis naïve). Total and Plasmodium falciparum apical membrane antigen-1 (AMA1) and glutamate rich protein-R0 (GLURP-R0) specific IgM, IgG and IgG subclass concentrations was measured in 129 and 52 of recruited HIV-infected and uninfected individuals, respectively. In addition, HIV-1 viral load (VL), CD4+ T cell count, and C-reactive protein (CRP) concentration was quantified in study participants. Antibody levels were compared based on HIV status and the associations of antibody concentration with HIV-1 VL, CD4+ count, and CRP levels was measured using Spearman correlation testing. RESULTS: Among study participants, concentrations of IgM, IgG1 and IgG3 antibodies to AMA1 and GLURP-R0 were higher in HIV infected individuals compared to uninfected individuals (all p < 0.001). The IgG3 to IgG1 ratio to both AMA1 and GLURP-R0 was also significantly higher in HIV-infected individuals (p = 0.02). In HIV-infected participants, HIV-1 VL and CRP were weakly correlated with AMA1 and GLURP-R0 specific IgM and IgG1 concentrations and total (not antigen specific) IgM, IgG, IgG1, and IgG3 concentrations (all p < 0.05), suggesting that these changes are related in part to viral load and inflammation. CONCLUSIONS: Overall, HIV infection leads to a total and malaria antigen-specific immunoglobulin production bias towards higher levels of IgM, IgG1, and IgG3, and HIV-1 viraemia and systemic inflammation are weakly correlated with these changes. Further assessments of antibody affinity and function and correlation with risk of clinical malaria, will help to better define the effects of HIV infection on clinical and biological immunity to malaria.

Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: study design and methodology for a cluster randomized controlled trial.

Most human Plasmodium infections in western Kenya are asymptomatic and are believed to contribute importantly to malaria transmission. Elimination of asymptomatic infections requires active treatment approaches, such as mass testing and treatment (MTaT) or mass drug administration (MDA), as infected persons do not seek care for their infection. Evaluations of community-based approaches that are designed to reduce malaria transmission require careful attention to study design to ensure that important effects can be measured accurately. This manuscript describes the study design and methodology of a cluster-randomized controlled trial to evaluate a MTaT approach for malaria transmission reduction in an area of high malaria transmission. Ten health facilities in western Kenya were purposively selected for inclusion. The communities within 3 km of each health facility were divided into three clusters of approximately equal population size. Two clusters around each health facility were randomly assigned to the control arm, and one to the intervention arm. Three times per year for 2 years, after the long and short rains, and again before the long rains, teams of community health volunteers visited every household within the intervention arm, tested all consenting individuals with malaria rapid diagnostic tests, and treated all positive individuals with an effective anti-malarial. The effect of mass testing and treatment on malaria transmission was measured through population-based longitudinal cohorts, outpatient visits for clinical malaria, periodic population-based cross-sectional surveys, and entomological indices.

Provider knowledge of treatment policy and dosing regimen with artemether-lumefantrine and quinine in malaria-endemic areas of western Kenya.

BACKGROUND: Due to widespread anti-malarial drug resistance in many countries, Kenya included, artemisinin-based Combination Therapy (ACT) has been adopted as the most effective treatment option against malaria. Artemether-lumefantrine (AL) is the first-line ACT for treatment of uncomplicated malaria in Kenya, while quinine is preferred for complicated and severe malaria. Information on the providers' knowledge and practices prior to or during AL and quinine implementation is scanty. The current study evaluated providers' knowledge and practices of treatment policy and dosing regimens with AL and quinine in the public, private and not-for-profit drug outlets. METHODS: A cross-sectional survey using three-stage sampling of 288 (126 public, 96 private and 66 not-for-profits) providers in drug outlets was conducted in western Kenya in two Plasmodium falciparum-endemic regions with varying malarial risk. Information on provider in-service training, knowledge (qualification, treatment policy, dosing regimen, recently banned anti-malarials) and on practices (request for written prescription, prescription of AL, selling partial packs and advice given to patients after prescription), was collected. RESULTS: Only 15.6% of providers in private outlets had received any in-service training on AL use. All (100%) in public and majority (98.4%) in not-for-profit outlets mentioned AL as first line-treatment drug. Quinine was mentioned as second-line drug by 47.9% in private outlets. A total of 92.0% in public, 57.3% in private and 78.8% in not-for-profit outlets stated correct AL dose for adults. A total of 85.7% of providers in public, 30.2% in private and 41.0% in not-for-profit outlets were aware that SP recommendations changed from treatment for mild malaria to IPTp in high risk areas. In-service training influenced treatment regimen for uncomplicated malaria (P = 0.039 and P = 0.039) and severe malaria (P < 0.0001 and P = 0.002) in children and adults, respectively. Most (82.3%) of private outlets sell partial packs of AL while 72.4% do not request for written prescription for AL. In-service training influenced request for written prescription (P = 0.001), AL prescription (P < 0.0001) and selling of partial packs (P < 0.0001). CONCLUSION: Public-sector providers have higher knowledge on treatment policy and dosing regimen on recommended anti-malarials. Changes in treatment guidelines should be accompanied by subsequent implementation activities involving all sector players in unbiased strategies.

Knowledge and behaviour as determinants of anti-malarial drug use in a peri-urban population from malaria holoendemic region of western Kenya.

BACKGROUND: The appropriate use of anti-malarial drugs determines therapeutic efficacy and the emergence and spread of drug-resistant malaria. Strategies for improving drug compliance require accurate information about current practices at the consumer level. This is to ascertain that the currently applied new combination therapy to malaria treatment will achieve sustained cure rates and protection against parasite resistance. Therefore, this cross-sectional study was designed to determine knowledge and behaviour of the consumers in households (n = 397) in peri-urban location in a malaria holoendemic region of western Kenya. METHODS: The knowledge and behaviour associated with anti-malarial use were evaluated. Using clusters, a questionnaire was administered to a particular household member who had the most recent malaria episode (within <2 weeks) and used an anti-malarial for cure. Mothers/caretakers provided information for children aged <13 years. RESULTS: Consumers' knowledge on dosage and duration/frequency demonstrated that only 29.4% used the correct artemisinin-based combination therapy (ACT) dosage. Most respondents who used quinine identified the correct duration of use (96.4%) since its administration was entirely at health facilities. To assess behaviours during use of anti-malarial drugs, respondents were stratified into those who took drugs with prescription (39.4%) and without prescription (61.6%). For those without prescription, the reasons given were; procedure of acquisition less costly (39.0%), took same drug for similar symptoms (23.0%), not satisfied with health services (15.5%), neighbour/friend/relative previously taken the same drug (12.5%) and health institution was far from their location (10%). CONCLUSION: Majority of consumers in the study area were knowledgeable on the symptoms of malaria. In addition, majority acquired ineffective anti-malarial drugs for treatment and reported sub-optimal treatment regimens with the currently recommended drugs. Furthermore, behaviours which constrain the successful up-scaling of ACT were common, creating a challenge in the desire to turn efficacy to effectiveness of the combination therapy programme. It will be important to direct and focus interventions in creating awareness on the importance of using recommended drugs to lessen the use of less efficacious anti-malarials. In addition, the consumers need to be educated on the importance of drug adherence in such areas to reduce the emergence and spread of drug-resistant malaria.

Factors determining anti-malarial drug use in a peri-urban population from malaria holoendemic region of western Kenya.

BACKGROUND: Interventions to reverse trends in malaria-related morbidity and mortality in Kenya focus on preventive strategies and drug efficacy. However, the pattern of use of anti-malarials in malaria-endemic populations, such as in western Kenya, is still poorly understood. It is critical to understand the patterns of anti-malarial drug use to ascertain that the currently applied new combination therapy to malaria treatment, will achieve sustained cure rates and protection against parasite resistance. Therefore, this cross-sectional study was designed to determine the patterns of use of anti-malarial drugs in households (n = 397) in peri-urban location of Manyatta-B sub-location in Kisumu in western Kenya. METHODS: Household factors, associated with the pattern of anti-malarials use, were evaluated. Using clusters, questionnaire was administered to a particular household member who had the most recent malaria episode (within <2 weeks) and used an anti-malarial for cure. Mothers/caretakers provided information for children aged <13 years. RESULTS: Stratification of the type of anti-malarial drugs taken revealed that 37.0% used sulphadoxine/pyrimethamine (SP), 32.0% artemisinin-based combined therapy (ACT), 11.1% anti-pyretics, 7.3% chloroquine (CQ), 7.1% quinine, 2.5% amodiaquine (AQ), while 3.0% used others which were perceived as anti-malarials (cough syrups and antibiotics). In a regression model, it was demonstrated that age (P = 0.050), household size (P = 0.047), household head (P = 0.049), household source of income (P = 0.015), monthly income (P = 0.020), duration of use (P = 0.029), dosage of drugs taken (P = 0.036), and source of drugs (P = 0.005) significantly influenced anti-malarial drug use. Overall, 38.8% of respondents used drugs as recommended by the Ministry of Health. CONCLUSION: This study demonstrates that consumers require access to correct and comprehensible information associated with use of drugs, including self-prescription. There is potential need by the Kenyan government to improve malaria care and decrease malaria-related morbidity and mortality by increasing drug affordability, ensuring that the recommended anti-malarial drugs are easily available in all government approved drug outlets and educates the local shopkeepers on the symptoms and appropriate treatment of malaria. Following a switch to ACT in national drug policy, education on awareness and behaviour change is recommended, since the efficacy of ACT alone is not sufficient to reduce morbidity and mortality due to malaria.

Prevalence and characterization of Escherichia coli O157:H7 isolates from meat and meat products sold in Amathole District, Eastern Cape Province of South Africa.

Meat and meat products have been implicated in outbreaks of Escherichia coli O157:H7 in most parts of the world. In the Amathole District Municipality of the Eastern Cape Province of South Africa, a large number of households consume meat and meat products daily, although the microbiological quality of these types of food is questionable. The present study investigated the prevalence of E. coli O157:H7 isolated from selected meat and meat products (45 samples each of biltong, cold meat, mincemeat, and polony) sold in this area. Strains of E. coli O157:H7 were isolated by enrichment culture and confirmed by polymerase chain reaction (PCR). Also investigated were the antibiogram profiles of the E. coli O157:H7 isolates. Five (2.8%) out of 180 meat and meat products examined were positive for E. coli O157:H7 that carried the fliC(H7), rfbE(O157), and eaeA genes. Two of the E. coli O157:H7 isolates were resistant against all the eight antibiotics tested. To prevent E. coli O157:H7 infections, meat and meat products such as biltong, cold meat, mincemeat and polony should be properly handled, and packed in sterile polyvinyl wrappers.