Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya.

Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization.

MOLECULAR CHARACTERISATION OF ECHINOCOCCUS GRANULOSUS SPECIES/STRAINS IN HUMAN INFECTIONS FROM TURKANA, KENYA.

BACKGROUND: Cystic echinococcosis (CE) or hydatid disease is a neglected, economically important zoonotic disease endemic in pastoralist communities, in particular the Turkana community of Kenya. It is caused by the larval stage of the highly diverse species complex of Echinococcusgranulosus sensu lato (s.l). The situation on the genetic diversity in humans in Kenya is not well established. OBJECTIVE: To characterise Echinococcus granulosus (s.1) species/strains isolated from humans undergoing surgery in Turkana, Kenya. DESIGN: A Cross sectional study. SETTING: The Kakuma Mission Hospital and Centre for Microbiology Research, Kenya Medical Research Institute. SUBJECTS: Eighty (80) parasite samples from 26 subjects were analysed by Polymerase chain reaction--Restriction fragment length polymorphism (PCR-RFLP) targeting the nad 1 gene for molecular characterization. RESULTS: Two different genotypes of E. granulosus were identified from the samples analysed: E. granulosus sensu stricto (G1-G3) 85% of the samples analysed and E. canadensis G6/7 (15%). Most of the hydatid cysts (35%) were isolated from the liver. Other sites where cysts were isolated from include: kidney, abdomen, omentum, retroperitonium and the submandibular. Majority of cysts presented as CE1 (50%) and CE3B (42%) images according to WHO ultrasound classification. Both males and females were infected with E. granulosus s.s but only the females showed infection with E. canadensis G6/7. Chi-square test revealed significant difference between age of individuals and cysts classification by ultrasound. In addition, there was an association between cyst presentation (single or multiple) and genotype whereby all the E. canadensis G6/7 cases presented as single cysts in the infected persons. CONCLUSION: This study corroborates previous reports that E. canadensis G6/7 strain is present in Turkana, a place where initially only E. granulosus s.s (G1-G3) was known to be present and that E. granulosis (G1-G3) remains the most widespread genotype infecting humans in the Turkana community.

Evaluation of effectiveness of diethylcarbamazine/albendazole combination in reduction of Wuchereria bancrofti infection using multiple infection parameters.

OBJECTIVES: To evaluate the effect of multiple rounds of annual single dose of DEC (6 mg/kg) or albendazole (400mg) given alone or in combination on Wuchereria bancrofti microfilaraemia, anti-filarial IgG1 and IgG4 and antigenaemia. METHODS: A total of 170 participants were randomly assigned to albendazole (n = 62), DEC (n = 54), and DEC plus albendazole (DEC/ALB) combination (n = 54). Blood samples were collected at pre-treatment in 1998, at 1 week and 6 months after the first treatment and thereafter before subsequent treatments in 1999 and 2000. Effects of treatment on W. bancrofti infection were determined by changes in levels of microfilaraemia, antifilarial antibodies and circulating filarial antigen. RESULTS: Comparison of geometric mean microfilariae intensities between DEC/ALB combination and DEC or albendazole single therapy groups after two rounds of annual treatment and 24 months follow-up showed that combination therapy resulted in a greater reduction of microfilaraemia than single therapy with either albendazole (p < 0.001) or DEC alone (p = 0.146). The overall levels of anti-filarial antibodies decreased significantly (p = 0.028 for IgG1 and p < 0.043 for IgG4) in all treatment groups at 24 months follow-up. Additionally, overall reduction in geometric mean circulating filarial antigen levels at 24 months was 44%, 60% and 85% for albendazole, DEC and DEC/ALB groups, respectively. CONCLUSIONS: These study findings suggest that albendazole improved efficacy of DEC and mass administration of a combination of the two drugs would therefore enhance the interruption of transmission of W. bancrofti in endemic areas. This information has important implications for the ongoing Global Program for Elimination of Lymphatic Filariasis.

Oxacillin resistant Staphylococcus aureus among HIV infected and non-infected Kenyan patients.

BACKGROUND: Infections due to methicillin resistant S. aureus (MRSA) present global challenges to clinicians since therapeutic options are limited and suboptimal dosing contributes to heightened mortality and increased length of hospital stay particularly among the HIV infected patients. OBJECTIVES: To assess the prevalence and relative risk of MRSA infections in HIV infected patients. DESIGN: Cross sectional analytical study. SETTING: Kenya Medical Research Institute, Opportunistic Infection Laboratories in Nairobi. SUBJECTS: Four hundred and thirty six male and female patients aged one to 65 years, of whom 220 were HIV-infected and 216 were non-infected. RESULTS: There was 436 male (57.1%) and female (42.9%) respondents. The prevalence of MRSA was 26.3% with majority infecting the HIV infected patients (P=0.046). Likewise, the overall Staphylococcal infections were more common in HIV patients (P <0.001). The common test for MRSA oxacillin disk diffusion had a sensitivity and specificity of 100% and 92%. CONCLUSION: HIV is a predisposing factor to Staphylococcal infection and there are indications that treatment with beta-lactam antibiotics may no longer be relied on as sole empiric therapy for several ill HIV patients whose infections may be of MRSA in origin. There is need for an informed choice in administration of appropriate antibiotics in order to minimise treatment failures due to the multidrug resistance and Vanvomycin intermediate S. aureus (VISA) strains. Molecular epidemiology of MRSA strains in understanding new and emerging trends is recommended.

Biochemical changes in cerebrospinal fluid of Chlorocebus aethiops naturally infected with zoonotic Meningonema peruzzii.

BACKGROUND: Thirty-four wild Chlorocebus aethiops monkeys were trapped for research purposes. METHODS: During routine quarantine check-up, cerebrospinal fluid (CSF) and blood were microscopically examined for parasites. Estimations of CSF protein levels were made by the biuret method and the white cell counts by the hemocytometer. RESULTS: Seven monkeys demonstrated microfilariae in blood and CSF. This was accompanied by a two- and ninefold increase in CSF total protein and white cell counts, respectively. Necropsy of one of the blood and CSF microfilariae-positive animals revealed the presence of adult worms in the brain meninges. The parasites were identified as the zoonotic filaroid nematode Meningonema peruzii. CONCLUSIONS: Wild C. aethiops monkeys developed CSF changes resulting, most probably, from infection with M. peruzii. Moreover, the monkeys could be acting as an important reservoir. The study highlights the need for epidemiological and pathogenological studies of this parasite, which is of public health significance. Moreover, C. aethiops proved to be a useful primate model for the study of this zoonotic infection.

Impact of two rounds of mass treatment with diethylcarbamazine plus albendazole on Wuchereria bancrofti infection and the sensitivity of immunochromatographic test in Malindi, Kenya.

Annual single-dose mass treatment of endemic populations with a combination of either diethylcarbamazine (DEC) or ivermectin plus albendazole is recommended as the mainstay of lymphatic filariasis elimination programmes. We evaluated the impact of two rounds of annual mass drug administration (MDA) of DEC and albendazole on bancroftian filariasis in a pilot elimination programme in an endemic area of Kenya. Overall prevalence of microfilaraemia decreased by 65.4%, whereas community microfilarial load decreased by 84% after the two MDAs. The prevalence of parasite antigenaemia determined by immunochromatographic test (ICT) declined significantly by 43.5% after the two MDAs. We also studied the effect of mass treatment on the sensitivity of the ICT. Although the sensitivity of the test before treatment was high (89.9%; kappa=0.909) sensitivity was lower after two MDAs (59.3%; kappa=0.644). The finding raises concern about the reliability of the ICT in long-term monitoring of infection and for establishing programmatic endpoints. The results of the present study indicate a relatively high effectiveness of MDA using a DEC/albendazole combination against Wuchereria bancrofti infection and, therefore, it may be a useful strategy to eliminate lymphatic filariasis in onchocerciasis-free areas.

Immuno-parasitological assessment of bancroftian filariasis in a highly endemic area along the River Sabaki, in Malindi district, Kenya.

Lymphatic filariasis is endemic in the coastal areas of Kenya, with four major foci identified in the early 1970s. The prevalence and intensity of Wuchereria bancrofti infection, together with antifilarial antibody responses, were assessed in a historically highly endemic focus along the River Sabaki, in Malindi district. The prevalences of microfilaraemia and antigenaemia (detected by Og4C3 ELISA) were >20% and >40%, respectively, and both increased steadily with age. The high prevalences of antifilarial IgG1 (86%) and IgG4 (91%) responses indicate that most people living in this setting are exposed to W. bancrofti infection. The children investigated had higher levels of antifilarial IgG1 than the adults. The results of this study, based on a battery of currently available parasitological and immunological methods, provide an epidemiological update on lymphatic filariasis on the northern Kenyan coast. They show that the River Sabaki area is still an important focus for bancroftian filariasis and highlight the importance of implementing an elimination programme, to interrupt the transmission of W. bancrofti in all areas of endemicity in Kenya. The detailed baseline data collected in the River Sabaki area make the communities studied ideal as sentinel sites for epidemiological monitoring and the evaluation of the impact of mass drug administrations to eliminate lymphatic filariasis.

Chronic clinical manifestations related to Wuchereria bancrofti infection in a highly endemic area in Kenya.

Clinical examinations were conducted in an effort to provide baseline data for a pilot filariasis elimination programme implemented in a Wuchereria bancrofti-endemic focus in Malindi district, Kenya. Of 186 males aged 15 years and above examined, 64 individuals (34.4%) had hydrocele, and the prevalence of the manifestation in those above 40 years old was 55.3%. The prevalence of leg lymphoedema in persons aged 15 years and above was 8.5%, with a higher rate in males (12.6%) than in females (5.7%). The overall prevalence of inguinal adenopathy was 8.6%, and males had a significantly higher (12.9%) prevalence of adenopathy than females (5.1%) (P<0.001). The data in the present study provided support for consideration of filarial infection as a possible cause of inguinal lymphadenopathy in bancroftian filariasis-endemic areas. The results of this study also indicate that lymphatic filariasis is a serious public health problem in the northern coastal areas and morbidity control programmes should be implemented to alleviate the suffering of those affected.

Evaluation of the Integrated Management of Childhood Illness guidelines for treatment of intestinal helminth infections among sick children aged 2-4 years in western Kenya.

Anthelmintic treatment of sick preschool-age children at health facilities is a potentially effective strategy for intestinal helminth control in this age-group. We conducted a study from July 1998 to February 1999 in western Kenya to determine whether the Integrated Management of Childhood Illness (IMCI) guidelines' clinical assessment can be used to identify helminth-infected children, and to evaluate the nutritional benefit of treating sick children without pallor with an anthelmintic (mebendazole is already part of IMCI treatment for sick children aged 2-4 years with palmar pallor in areas where hookworm and Trichuris trichiura infections are endemic). Sick children aged 2-4 years seen at 3 rural health facilities were clinically evaluated and tested for haemoglobin concentration, malaria parasites, and intestinal helminths. Children without pallor were randomly assigned to receive a single dose of 500 mg of mebendazole or a placebo and re-examined 6 months later. Among the 574 children enrolled, 11% had one or more intestinal helminths. Most infections were of light intensity. Selected clinical signs and symptoms available from the IMCI assessment, including palmar pallor and low weight-for-age, were not associated with helminth infection. Six months after enrollment, no differences in growth of children without pallor were observed between the mebendazole (n = 166) and placebo (n = 181) groups. However, there was a significantly greater mean increase in weight, height, and weight-for-age Z score among the helminth-infected children in the mebendazole group (n = 22) as compared with helminth-infected children in the placebo group (n = 20). We conclude that even lightly infected preschool-age children without palmar pallor benefit from anthelmintic treatment; however, in this study setting of low helminth prevalence and intensity, helminth-infected children could not be identified using the IMCI guidelines. Cost-effectiveness studies are needed to help define helminth prevalence thresholds for routine anthelmintic treatment of sick preschool-age children seen at first-level health facilities.

Evaluation of ICT filariasis card test using whole capillary blood: comparison with Knott's concentration and counting chamber methods.

An immunochromatographic card test (ICT) that uses fingerprick whole blood instead of serum for diagnosis of bancroftian filariasis has recently been developed. The card test was validated in the field in Kenya by comparing its sensitivity to the combined sensitivity of Knott's concentration and counting chamber methods. A total of 102 (14.6%) and 117 (16.7%) persons was found to be microfilaremic by Knott's concentration and counting chamber methods, respectively. The geometric mean intensities (GMI) were 74.6 microfilariae (mf)/ml and 256.5 mf/ml by Knott's concentration and counting chamber methods, respectively. All infected individuals detected by both Knott's concentration and counting chamber methods were also antigen positive by the ICT filariasis card test (100% sensitivity). Further, of 97 parasitologically amicrofilaremic persons, 24 (24.7%) were antigen positive by the ICT. The overall prevalence of antigenemia was 37.3%. Of 100 nonendemic area control persons, none was found to be filarial antigen positive (100% specificity). The results show that the new version of the ICT filariasis card test is a simple, sensitive, specific, and rapid test that is convenient in field settings.

Lymphatic filariasis in kenya since 1910, and the prospects for its elimination: a review.

OBJECTIVES: To provide an overview of lymphatic filiariasis in Kenya from the first time its prevalence was reported to the present day, with suggestions of issues that are yet to be resolved and to present the prospects for its elimination. DATA SOURCES: Published and unpublished reports on filariasis studies in Kenya. STUDY SELECTION: Field-based epidemiological studies covering aspects of clinical, parasitology, entomology, social, economic, diagnosis and control of filariasis. DATA EXTRACTION: Review of published articles in scientific journals and communications, retrieval and review of published scientific articles from the Internet and personal communications. DATA SYNTHESIS: Re-organisation and pooling retrieved published data. CONCLUSIONS: Almost one century after the first documented report of lymphatic filariasis in Kenya, no National Control Programme has been instituted. However, important findings that have implications on its control have been made and they should be utilised to implement a National Control Programme. On implementation of the National Control Programme, research should be focussed on the remaining unresolved issues and conducted within the framework of the Programme. The World Health Organisation has targeted lymphatic filariasis for global elimination by the year 2020. Kenya is well positioned to formulate her National Plan for Elimination of Lymphatic Filariasis (NPELF) and join other endemic countries worldwide, which have already launched their plans, in the global efforts to eliminate lymphatic filariasis as a public health problem.

Hydrocelectomy: a proxy for hydrocele prevalence in coastal Kenya.

To assess the value of hydrocelectomy as an indicator of the prevalence of lymphatic filariasis, the frequency of hydrocelectomy was investigated in five hospitals in an area of coastal Kenya where filariasis is endemic. Two of the hospitals studied (Kinango and Msambweni) were in Kwale district, two (Kilifi and Malindi) in Kilifi district and one (the Coast Provincial General Hospital) in Mombasa. Surgical operations performed between January 1991 and August 1993 were tallied from the main theatre registers. Additionally, admission files for hydrocelectomy patients were examined prospectively between September 1993 and February 1994, to obtain age profiles. Hydrocelectomies accounted for 27.6%, 16.6%, 13.6%, 4.3% and 2.0% of the major operations (totalling 6339) recorded in Kinango, Msambweni, Kilifi, Malindi and Coast Provincial General Hospital, respectively. The proportion of operations involving hydrolectomy was significantly higher in the two hospitals in Kwale district, in the southern part of the study area, than in the two hospitals in Kilifi district, in the northern part (23.4%, with 95% confidence intervals of 20.9%-25.9%, v. 10.3%, with 95% confidence intervals of 8.7%-11.9%; P < 0.001). The generally high frequencies of hydrocelectomy in the study area are evidence of the heavy social and economic burden imposed by hydrocele-attributable morbidity and its management. The age distribution pattern of the hydrocelectomy patients paralleled that of the individuals with hydrocele in the surrounding area.

An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis.

This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole + ivermectin or albendazole + diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90,635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n = 1538), ivermectin (9822), DEC (576), albendazole + ivermectin (7470), albendazole + DEC (69,020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80-90% of the 'at risk' populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin + albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.

Wuchereria bancrofti in Kwale District, Coastal Kenya: patterns of focal distribution of infection, clinical manifestations and anti-filarial IgG responsiveness.

A cross-sectional study of bancroftian filariasis was conducted in 2 adjacent communities, Mvumoni and Kilore in Muhaka, Kwale District. Wuchereria bancrofti infection, clinical manifestations and anti-filarial IgG responsiveness were determined before the long rains, a time coinciding with a low transmission season. The prevalence of microfilaraemia increased gradually with age and was significantly higher in Kilore (24%) than in Mvumoni (6.3%, P < 0.001). Similarly, the prevalence of antigenaemia increased with age and also was significantly higher in Kilore, 48.9% than in Mvumoni, 20.5% (P < 0.001). Hydrocele, funiculitis, lymphangitis and lymphadenitis were also significantly more common in Kilore than in Mvumoni. In comparing the 2 communities, levels of IgG4 responsiveness in antigen-positive persons were higher in Kilore than Mvumoni (P = 0.034), but this was related to higher antigen loads in persons in Kilore than in Mvumoni. In antigen-negative persons, anti-filarial antibodies of 3 IgG isotypes were significantly higher in Kilore than Mvumoni (P < 0.001, for IgG1, IgG2, IgG4). These results emphasize the highly focal nature of bancroftian filariasis in this setting and demonstrate that anti-filarial antibody levels are related to transmission intensity.

Bancroftian filariasis: profile of serum antifilarial antibody and circulating parasite antigen.

Forty-five serum specimens collected from persons living in a filaria-endemic community in Maili Nane, Coastal Kenya were analyzed by ELISA for levels of isotype specific antifilarial antibody and by Og4C3 ELISA for circulating parasite antigen. Mean levels of IgG1, IgG2, and IgG3 were lower in microfilaraemic persons than in amicrofilaraemic individuals. In contrast, mean levels of antifilarial IgG4 were significantly higher in microfilaraemic persons (p = 0.0374). Serum samples from all microfilaremic persons were positive for circulating antigen as were 15% of samples from amicrofilaremic and asymptomatic persons. The Og4C3 antigen assay may have value as a technique for identifying and targeting communities for control efforts.

Advances in the diagnosis of human lymphatic filariases: a review.

The nematode parasites Wuchereria bancrofti, Brugia malayi and B. timori are the causative agents of human lymphatic filariasis. Of the estimated 90 million infections world-wide, W. bancrofti is responsible for over 80 million cases and is the only known aetiologic agent in the African Region. Numbers of infected persons are on the increase world-wide due to rural-urban migrations which result in mushrooming of shanty towns often encouraging formation of favourable mosquito breeding-sites. Development of insecticide resistance by the vector mosquitoes; the toxicity and high cost of available effective formulations, and the deteriorating global economy aggravate this situation. Human lymphatic filariasis is more of a morbidity than a mortality-causing disease but can be devastating and crippling at both the individual and community levels. Unlike many parasitic infections, lymphatic filariasis can easily be controlled. The success of any control programme depends on sensitive diagnostic techniques and this is the challenge. Identification of all true positive individuals in an endemic community can be problematic since filariasis is spectral and no single diagnostic technique can be expected to be uniformly sensitive in all situations. Availability of new biotechnologies has given impetus to formulations of several diagnostic tools. New diagnostic methods and improvements on the traditional ones is the topic of this review. Recommendations in view of their field applications are also discussed.