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Biomedical subjects

M Mugambi

Publications and source records attributed to M Mugambi.

At least 19 recordsLinked to original sources

Serological evidence of arboviral infections among humans of coastal Kenya.

A serosurvey was conducted during September 1987 for evidence of human arboviral infections in the Coast Province of Kenya. Sera were collected from 1624 outpatients at three hospitals and tested for antibody to eight arboviruses by the indirect immunofluorescent antibody technique. Antibody prevalence rates were: Rift Valley fever, 2.8%; Sindbis, 2.6%; dugbe, 2.1%; dengue-2, 1.0%; West Nile, 0.9%; chikungunya, 0.7% and Nairobi sheep disease, 0.3%. Evidence of Crimean-Congo haemorrhagic fever viral antibody was not detected. The data suggested low arbovirus activity since 1982, when an epidemic of dengue occurred in this region, and revealed the first evidence of dugbe viral infection among humans in Kenya.

Adolescent↗

The Kenyan Luo migration study: observations on the initiation of a rise in blood pressure.

OBJECTIVE: To demonstrate the magnitude, timing, and cause of changes in blood pressure that occur in migrants from a low blood pressure population on moving to an urban area. DESIGN: A controlled longitudinal observational study of migrants as soon after migration as possible and follow up at three, six, 12, 18, and 24 months after migration. A cohort of controls living in a rural area who were matched for age, sex, and locality were also observed at the same periods. SETTING: 35 Villages on the northern shores of Lake Victoria in western Kenya and Nairobi. PARTICIPANTS: 325 Members of the Luo tribe aged 15 to 34 years who had migrated to Nairobi and 267 controls living in villages. The numbers of both groups reduced during follow up such that only 63 migrants and 143 controls were followed up for two years. MAIN OUTCOME MEASURES: A medical questionnaire and three 24 hour diet histories were completed by migrants and controls. Height, weight, pulse, and blood pressure were measured. Three 12 hour overnight urine samples were collected from all participants and analysed for sodium, potassium, and creatinine concentrations. RESULTS: The mean systolic blood pressure of migrants was significantly higher than that of controls throughout the study, and the distribution of blood pressure was shifted to the right compared with controls. The mean diastolic blood pressure of the two groups diverged over time. Blood pressure differences were not due to selective migration. The migrants' mean urinary sodium:potassium ratio was higher than that of controls (p less than 0.001) throughout, and weight and pulse rate were also higher among migrants, although differences diminished with time. CONCLUSIONS: Urinary sodium:potassium ratio, pulse rate, and weight are important predictors of increased blood pressure among migrants from a low blood pressure community and may also be implicated in the initiation of essential hypertension.

Adolescent↗

Human lymphocyte proliferative response to a sporozoite T cell epitope correlates with resistance to falciparum malaria.

To identify vaccine relevant T cell epitopes on the circumsporozoite (CS) protein of Plasmodium falciparum, the lymphocyte proliferative responses to 10 CS protein derived peptides were studied in 28 adult Kenyans, and correlated with resistance to malaria. Eight peptides, six of which were not overlapping, induced proliferation of lymphocytes from one to five volunteers, suggesting either genetic restriction of response to each of the T epitopes, or dominance of some T sites on the immunizing sporozoites. The 28 volunteers were radically cured of malaria and during the next 126 days 25 of the 28 were reinfected. Resistance to malaria was not correlated with antibodies to malaria Ag, but was significantly correlated with lymphocyte responses to CS protein residues 361-380 and 371-390. Among the 25 volunteers who became re-infected with malaria, lymphocytes from only two responded to a peptide including residues 361-380 of the P. falciparum CS protein, and only one to peptide 371-390. In contrast, lymphocytes from all three volunteers who did not become infected responded to peptide 361-380 (p = 0.003), and lymphocytes from two of the three responded to peptide 371-390 (p = 0.023). The significant correlation between proliferation to peptides 361-380 and 371-390 and resistance to malaria suggests that at least one epitope within these overlapping peptides is involved in a protective cellular immune response. The data support inclusion of these residues in future CS protein vaccines.

Adult↗

Epidemiology of hepatitis B in eastern Kenya.

A cross-sectional survey of outpatients attending the three distinct hospitals in the towns of Mombasa, Kilifi, and Malindi was conducted to determine the patterns of hepatitis B transmission in eastern Kenya. Of 1,533 study subjects (mean age 21.9 +/- 13.2 years; range, 4 months to 80 years), 11.4% were positive for HBsAg and 56.2% were seropositive for at least one hepatitis B marker (HBsAg, anti-HBs, or anti-HBc). Anti-delta antibody was found in 1.2% of HBsAg-positive samples. HBeAg was found in 36.0% of HBsAg-positive samples obtained from women of childbearing age. The prevalence of seropositivity for hepatitis B markers was positively correlated with age, increasing from 20% in subjects less than 4 years old to more than 80% in study subjects greater than 40 years old. On multivariate analysis, male sex was found to be associated with HBsAg positivity, and age and previous deliveries of children were associated with seropositivity for any hepatitis marker (HBsAg, anti-HBs, or anti-HBc). An effective hepatitis B immunization strategy in this region of Kenya would require vaccination early in life because a major portion of hepatitis B transmission occurs in childhood.

Adolescent↗

Plasmodium falciparum: DNA probe diagnosis of malaria in Kenya.

We previously reported isolation of DNA probe which specifically recognizes Plasmodium falciparum and developed a simple method for its use. The sensitivity and specificity of this DNA probe method have now been extensively field tested in comparison with those of conventional microscopic examination of blood films in two separate studies in Malindi, Kenya, involving a total of 1179 patients. In the second study, which used improved techniques, sensitivity of the DNA probe was 89% when compared to microscopy. We conclude that the DNA probe method compares favorably with conventional microscopy in detecting parasite densities as low as 25 parasites per microliter of blood. A significant advantage of the DNA probe method is that it utilizes a standardized procedure which can simultaneously and reproducibly analyze a large number of samples without opportunity for significant reader bias.

Adult↗

Predisposition of humans to infection with Schistosoma mansoni: evidence from the reinfection of individuals following chemotherapy.

In a study of faecal egg counts of Schistosoma mansoni from 359 people of all ages from a rural Kenyan community, a positive association was demonstrated between infection intensity in individuals before treatment and reinfection intensity in the same individuals 9 months after treatment in certain age groups of the sampled population. Consequences and possible causes of these observations are discussed in terms of the epidemiology and control of schistosomiasis.

Adolescent↗

Naturally acquired antibodies to sporozoites do not prevent malaria: vaccine development implications.

The first human vaccines against the malaria parasite have been designed to elicit antibodies to the circumsporozoite protein of Plasmodium falciparum. However, it is not known whether any level of naturally acquired antibodies to the circumsporozoite protein can predict resistance to Plasmodium falciparum malaria. In this study, 83 adults in a malaria-endemic region of Kenya were tested for circumsporozoite antibodies and then treated for malaria. They were monitored for the development of new malaria infections for 98 days. Antibody levels, as determined by four assays in vitro, were indistinguishable between the 60 individuals who did and the 23 who did not develop parasitemia during follow-up, and there was no apparent relation between day of onset of parasitemia and level of antibodies to circumsporozoite protein. Unless immunization with sporozoite vaccines induces antibodies that are quantitatively or qualitatively superior to the circumsporozoite antibodies in these adults, it is unlikely that such antibodies will prevent infection in areas with as intense malaria transmission as western Kenya.

Adult↗

Immunity after treatment of human schistosomiasis mansoni. III. Long-term effects of treatment and retreatment.

Group mean Schistosoma mansoni reinfection patterns are presented for 2 years after treatment with oxamniquine in 1981 of over 100 9- to 16-year-old Kenyan schoolchildren, and for one year after retreatment in 1983 with either oxamniquine or praziquantel when most (nearly 700) infected people in the whole community were treated. Quality control confirmed comparable Kato egg counts throughout the study. Continuing transmission after 1981 raised prevalence to nearly its original level within 6 months, but intensity remained suppressed throughout the 2 year follow-up and very few children reacquired heavy infections (greater than 400 eggs/g). Age and sex had significant effects: reinfection diminished with age, especially among boys--a pattern not apparently attributable to differential water contact. Children with heavy pretreatment infections tended to develop heavy reinfections but this trend was not statistically significant on a group basis, nor were similar trends during the period of less pronounced transmission following the 1983 community treatment. Oxamniquine was equally effective in children receiving it in both 1981 and 1983, and the efficacy of praziquantel resembled that of oxamniquine. In this area of Kenya, repeated chemotherapy will be needed to contain transmission, probably annually or biennially, unless supplemented with other, effective control measures. These findings confirm the beneficial effects of treating even a limited segment of a community at intervals of a year or more without necessarily stopping transmission. They are also compatible with recent findings on potential immune mechanisms in man.

Adolescent↗

Evidence for predisposition of individual patients to reinfection with Schistosoma mansoni after treatment.

Statistical analysis of the relationship between intensities of infection before treatment and during reinfection after treatment in a sample of 119 Kenyan schoolchildren demonstrated a positive association, indicating that the individuals differed consistently in their tendency to become infected. This association was stronger in young children but the trend was detectable in older individuals. Possible reasons for this variation and for its apparently greater influence in younger age groups are discussed.

Adolescent↗

Field evaluation of an enzyme-linked immunosorbent assay (ELISA) for Plasmodium falciparum sporozoite detection in anopheline mosquitoes from Kenya.

An enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody that recognizes a repetitive epitope on the circumsporozoite protein of Plasmodium falciparum was used in Kenya to assess malaria infections in Anopheles gambiae s.l. and An. funestus. The ELISA confirmed that 88% of 44 sporozoite-positive gland dissections were P. falciparum. The ELISA infection rate of 18.6% (n = 736) for individually tested mosquitoes for both species was significantly higher than the 10.4% (n = 537) salivary gland sporozoite rate determined by dissection. This difference was due to ELISA detection of medium and large sized oocysts on the midguts of infected mosquitoes which did not contain salivary gland sporozoites. From a series of 379 Anopheles that were cut at the thorax, ELISA tests on "head" and "body" portions showed that 29.5% of 95 positive mosquitoes contained circumsporozoite antigen in the body portion in the absence of salivary gland infections. This field evaluation demonstrates that the ELISA can most accurately be used to estimate sporozoite rates by cutting mosquitoes at the thorax and testing anterior portions.

Animals↗

Visceral leishmaniasis unresponsive to antimonial drugs. II. Response to high dosage sodium stibogluconate or prolonged treatment with pentamidine.

Ten Kenyan patients with visceral leishmaniasis unresponsive to sodium stibogluconate, at a dose of 16 to 20 mg Sb/kg body-weight/day given for 30 to 98 days, were treated with 20 mg Sb/kg bw given every eight hours. This regimen was modified or abandoned in six patients because of suspected toxicity, although toxicity was difficult to assess because of intercurrent illness. Toxic effects included lethargy, anorexia, vomiting, electrocardiographic changes, fall in haemoglobin and rise in liver enzymes. One patient died, probably from a cardiac arrhythmia. Two patients were cured, four responded partially and four showed no response. Pentamidine, at a dose of 4 mg/kg body-weight given one to 3 times per week for 5 to 39 weeks, was given as initial treatment in one patient and after failure of sodium stibogluconate in seven. Toxic effects included nephritis, hepatitis, transient diabetes and subcutaneous abscesses. Two patients were cured, two responded partially, three showed no response and one, after apparent cure, relapsed and was unresponsive to additional pentamidine treatment. Low-frequency, long-duration pentamidine was often useful in maintaining any improvement made during treatment with the less well tolerated high-dose, high frequency sodium stibogluconate. We observed the step-wise development of resistance to both sodium stibogluconate and pentamidine. The problems of managing patients with visceral leishmaniasis which is unresponsive to conventional doses of pentavalent antimonials are discussed and some tentative suggestions put forward.

Amidines↗

Blood pressure patterns in relation to age, weight and urinary electrolytes in three Kenyan communities.

The blood pressure patterns of three Kenyan communities have been studied: 861 members of the Luo tribe in a rural community, 281 members of the Kamba tribe in a rural community and 310 "urban" Luo living in Nairobi. The slope of linear regression of blood pressure with age was significantly different in each population: rural Luo had the smallest rise with age and urban Luo had the largest rise with age, while the Kamba tribe were in between. The differences could not be accounted for by weight. Urinary electrolyte data showed rural Luo had the lowest sodium ratios (sodium/creatinine, sodium/potassium) and the highest potassium/creatinine ratio: urban Luo had the highest sodium and lowest potassium ratios and rural Kamba had values in between. The differences in blood pressures between the two groups of the same tribe in different environments (rural and urban Luo) were far greater than those between different genetic groups (Kamba and Luo) underlining the importance of environmental factor(s) in the determination of arterial pressure. Furthermore, these data support the theory that the dietary intake of sodium and potassium are the major influential environmental factors affecting blood pressure.

Adolescent↗

Immunity after treatment of human schistosomiasis mansoni. II. Identification of resistant individuals, and analysis of their immune responses.

Intensities of re-infection were monitored at three-monthly intervals after treatment of Schistosoma mansoni infections in a group of 119 Kenyan schoolchildren, whose levels of water contact were also observed. 22 children showed high reinfection intensities (greater than 100 eggs per gram of faeces) by 12 months after treatment, and were considered to be susceptible. Out of 70 children who showed low reinfection intensities during the same period (less than 30 eggs per gram), 35 showed high levels both of total water contact and of contact with sites containing infected snails. In these children, the relative lack of reinfection could not be attributed to a lack of exposure, and they were classified as resistant to reinfection. Comparison of the two groups, resistant and susceptible, revealed no difference in pretreatment intensities of infection. However, there was a marked difference in age, the mean age of the resistant group being two years greater than that of the susceptible group, within a restricted starting age range. These findings indicated that resistance was an acquired and age-dependent phenomenon, not obviously related to previous egg-induced pathology. Studies of immune responses revealed no clearcut correlate of resistance, but there were interesting differences between the two groups. Whereas anti-egg antigen responses declined after treatment to a greater extent in the resistant than in the susceptible group, antibodies mediating eosinophil-dependent killing of schistosomula rose markedly in both groups, strongly suggesting that the resistant children were being exposed to cercariae. Anti-adult worm antibodies rose sharply in both groups immediately after treatment, and thereafter declined to pretreatment levels. Although some individual children showed high levels of IgE anti-schistosomulum antibodies, there were no significant differences between the two groups. Since all children showed detectable levels of antibodies mediating eosinophil-dependent killing of schistosomula, the possibility was considered that such antibodies might be a necessary, but not a limiting, factor in immunity. Instead, the functional state of the effector cells mediating antibody-dependent killing might be limiting. Eosinophil levels, measured as an indirect estimate of eosinophil functional activity, did not differ between the two groups. There were, however, marked differences between different individuals in their capacity to produce eosinophil-stimulating monocyte mediators, and although this cannot yet be related to resistance, this aspect is worth further study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Electrocardiographic changes during treatment of leishmaniasis with pentavalent antimony (sodium stibogluconate).

Serial electrocardiograms (ECGs) were obtained during 65 courses of sodium stibogluconate treatment in 59 Kenyan patients with leishmaniasis (56 visceral and 3 cutaneous). ECG abnormalities developed during 54% of the treatment courses. The frequency with which abnormalities occurred was related to the total daily dose of antimony (Sb), increasing from 2/9 patients treated with 10 mg Sb/kg/d to 25/48 treated with 20-30 mg Sb/kg/d and 8/8 treated with 40-60 mg Sb/kg/d. The frequency with which ECG abnormalities developed was also related to the duration of treatment, increasing from 11/65 patients after 7 days to 18/44 after 15 days, 26/39 after 30 days and 11/12 after 60 days. ECG abnormalities were similar to those previously described during treatment with trivalent antimonial drugs, the most common being flattening and/or inversion of T waves. Prolongation of the corrected QT interval occurred in 13 patients, all of whom were treated for more than 30 days or with more than 20 mg Sb/kg/d. One patient died suddenly during the fourth week of treatment with 60 mg Sb/kg/d, and 2 patients died of measles after 9 or 10 days of treatment with 30 mg Sb/kg/d. QT prolongation and a concave ST segment developed in all 3 patients who died. We conclude that minor ECG abnormalities are common when sodium stibogluconate is used at doses above 20 mg Sb/kg/d for more than 15 days, and that life-threatening arrhythmias may occur if very high doses are used.

Adolescent↗

Determinants of blood pressure changes due to urbanization: a longitudinal study.

Changes in blood pressure (BP) and associated factors which occur on migration from a rural to an urban environment are under observation in a longitudinal study. Blood pressures, heart rate (HR), urinary electrolytes, sociological and anthropometric data are recorded at 0, 3, 6, 12, 18 and 24 months following migration and compared with a cohort of age and sex-matched rural based controls. Data from the first 6 months' follow-up reveal that the migrants' BPs are higher and tend to rise compared with controls, in whom BP falls progressively with time. Changes in body weight and dietary electrolytes appear to explain some of the BP differences, while differences in pulse rates between groups suggest that a further mechanism operative through the autonomic nervous system is responsible for some of the elevation of systolic BP shown amongst migrants, particularly on arrival in the urban area.

Adult↗