Alcohol use, drunkenness and tobacco smoking in rural western Kenya.

OBJECTIVES: To describe the prevalence of smoking and alcohol use and abuse in an impoverished rural region of western Kenya. METHODS: Picked from a population-based longitudinal database of demographic and health census data, 72 292 adults (≥18 years) were asked to self-report their recent (within the past 30 days) and lifetime use of tobacco and alcohol and frequency of recent 'drunkenness'. RESULTS: Overall prevalence of ever smoking was 11.2% (11.0-11.5) and of ever drinking, 20.7% (20.4-21.0). The prevalence of current smoking was 6.3% (6.1-6.5); 5.7% (5.5-5.9) smoked daily. 7.3% (7.1-7.5) reported drinking alcohol within the past 30 days. Of these, 60.3% (58.9-61.6) reported being drunk on half or more of all drinking occasions. The percentage of current smokers rose with the number of drinking days in a month (P < 0.0001). Tobacco and alcohol use increased with decreasing socio-economic status and amongst women in the oldest age group (P < 0.0001). CONCLUSIONS: Tobacco and alcohol use are prevalent in this rural region of Kenya. Abuse of alcohol is common and likely influenced by the availability of cheap, home-manufactured alcohol. Appropriate evidence-based policies to reduce alcohol and tobacco use should be widely implemented and complemented by public health efforts to increase awareness of their harmful effects.

Access to HIV community services by vulnerable populations: evidence from an enhanced HIV/AIDS surveillance system.

HIV disproportionately affects vulnerable populations such as black and minority ethnic groups, men who have sex with men (MSM) and migrants, in many countries including those in the UK. Community organisations in the UK are charitable non-governmental organisations with a proportion of the workforce who volunteer, and provide invaluable additional support for people living with HIV (PLWHIV). Information on their contribution to HIV care in vulnerable groups is relatively sparse. Data generated from an enhanced HIV surveillance system in North West England, UK, was utilised for this study. We aimed to determine the characteristics of individuals who chose to access community services in addition to clinical services (1375 out of 4195 records of PLWHIV in clinical services). Demographic information, risk factors including residency status, uniquely gathered in this region, and deprivation scores were examined. Multivariate logistic regression modelling was conducted to predict the relative effect of patient characteristics on attendance at community services. Attendance at community services was highest in those living in the most, compared with least, deprived areas (p<0.001), and was most evident in MSM and heterosexuals. Compared to white UK nationals attendance was significantly higher in non-UK nationals of uncertain residency status (Adjusted odds ratio [AOR] = 21.91, 95% confidence interval [CI] 10.48-45.83; p<0.001), refugees (AOR = 5.75, 95% CI 3.3-10.03; p<0.001), migrant workers (AOR = 5.48, 95% CI 2.22-13.51; p<0.001) and temporary visitors (AOR = 3.44, 95% CI 1.68-7.05; p<0.001). Community services, initially established predominantly to support MSM, have responded to the changing demography of HIV and reach the most vulnerable members of society. Consequent to their support of migrant populations, community services are vital for the management of HIV in black and minority groups. Paradoxically, this coincides with increasing funding pressures on these services.

Acute presentations of HIV are still missed in low prevalence areas.

OBJECTIVES: To evaluate missed opportunities and delays in the diagnosis of HIV in a low prevalence setting over a 24 year period. METHODS: Patients with acute presentations of HIV were included in a retrospective note based review. Data were compared from acute presentations in 1985-2001 (88/241 new patients) with 2005-2007 (99/136 new patients). The number of recorded clinical and laboratory clues to infection and subsequent time delays to diagnosis of HIV were evaluated. RESULTS: The findings reflect the shifting demographics of HIV in the UK over the past two decades, exemplified by an eightfold increase in tuberculosis at presentation. Despite recording clinical stigmata of HIV (clues) in the notes, the number of missed clues increased, and many clinicians failed to request HIV testing. The median delay between presentation and diagnosis reduced from 5 to 1 day (p<0.001), and mortality dropped from 14% to 4% among patients presenting with acute symptoms. However, there was still a delay of more than 30 days before diagnosis for almost one in five patients. CONCLUSIONS: Despite some improvement and better awareness, there are still significant delays before hospital doctors consider the diagnosis of HIV for patients in low prevalence areas, even among some patient groups with high risk. Hospitals should consider moving to opt-out routine HIV testing of all medical admissions.

Progression of stunting and its predictors among school-aged children in western Kenya.

OBJECTIVE: The objectives of this study were (1) to assess whether a cohort of school-aged children experiences progression of stunting over a 2-y-period of observation and (2) to identify baseline nutritional and body composition risk factors for the progression of stunting. METHODS: As part of a large-scale, randomized controlled trial assessing the impact of insecticide-treated bednets (ITNs) on nutritional status, we longitudinally followed a cohort of school-aged children over a 2-y-period in western Kenya. Anthropometric measurements were made at four time points from which Z-scores for height-for-age (HAZ), weight-for-age (WAZ), and body mass index (BMIZ) were calculated. Two measures of body composition, upper arm fat area and upper arm muscle area, were derived from mid-upper arm circumference (MUAC) and triceps skinfold thickness. RESULTS: Subjects experienced a mean change in HAZ from baseline to 9 months of -0.16 [-0.19, -0.13], from baseline to 16 months of -0.18 [-0.22, -0.15], and from baseline to 24 months of -0.36 [-0.41, -0.31]. Thus, the average individual's change in HAZ at the three follow-up time points is significantly less than zero, meaning that, on average, the cohort is deviating further from NCHS reference medians over time. The baseline nutritional measure that explained the greatest amount of variance in the progression of stunting was the upper arm muscle area Z-score (F=8.1; P=0.005). CONCLUSIONS: This longitudinal study provides further evidence from a distinct ecological setting regarding the progression of undernutrition during middle childhood in the developing world. It suggests that school-aged children in the developing world do not experience catch-up growth or remain stable. Rather, they continue to deviate from NCHS standards, accruing greater height deficits with age. In addition, absolute lean body mass explained the most variability in the progression of stunting, which supports cross-sectional findings from other studies.

Transmission of epidemic Vibrio cholerae O1 in rural western Kenya associated with drinking water from Lake Victoria: an environmental reservoir for cholera?

Sub-Saharan Africa has the highest reported cholera incidence and mortality rates in the world. In 1997, a cholera epidemic occurred in western Kenya. Between June 1997 and March 1998, 14,275 cholera admissions to hospitals in Nyanza Province in western Kenya were reported. There were 547 deaths (case fatality rate = 4%). Of 31 Vibrio cholerae O1 isolates tested, all but one were sensitive to tetracycline. We performed a case-control study among 61 cholera patients and age-, sex-, and clinic-matched controls. Multivariate analysis showed that risk factors for cholera were drinking water from Lake Victoria or from a stream, sharing food with a person with watery diarrhea, and attending funeral feasts. Compared with other diarrheal pathogens, cholera was more common among persons living in a village bordering Lake Victoria. Cholera has become an important public health concern in western Kenya, and may become an endemic pathogen in the region.

All-cause mortality among young children in western Kenya. VI: the Asembo Bay Cohort Project.

Although all-cause mortality has been used as an indicator of the health status of childhood populations, such data are sparse for most rural areas of sub-Saharan Africa, particularly community-based estimates of infant mortality rates. The longitudinal follow-up of more than 1,500 children enrolled at birth into the Asembo Bay Cohort Project (ABCP) in western Kenya between 1992 and 1996 has provided a fixed birth cohort for estimating all-cause mortality over the first 5 yr of life. We surveyed mothers and guardians of cohort children in early 1999 to determine survival status. A total of 1,260 households were surveyed to determine the survival status of 1,556 live births (99.2% of original cohort, n = 1,570). Most mothers (66%) still resided but 27.5% had migrated, and 5.5% had died. In early 1999, the overall cumulative incidence of all-cause mortality for the entire 1992-1996 birth cohort was 26.5% (95% confidence interval, 24.1-28.9%). Neonatal and infant mortality were 32 and 176 per 1,000 live births, respectively. These community-based estimates of mortality in the ABCP area are substantially higher than for Kenya overall (nationally, infant mortality is 75 per 1,000 live births). The results provide a baseline description of all-cause mortality among children in an area with intense Plasmodium falciparum transmission and will be useful in future efforts to monitor changes in death rates attributable to control programs for specific diseases (e.g., malaria and HIV/AIDS) in Africa.

The safety of antimalarial drugs in pregnancy.

Alternative drugs to chloroquine are required to prevent the deleterious effects of malaria in pregnancy. Fear of potential toxicity has limited antimalarial drug use in pregnancy. Animal toxicity studies have documented teratogenicity when antimalarials are administered at high dosages. Excepting the tetracyclines, there is no evidence to suggest that, at standard dosages, any of the antimalarial drugs are teratogenic. Primaquine is not recommended because of the potential risk of haemolytic effects in the fetus. Rates of spontaneous abortion and birth defects were comparable in pregnant women taking mefloquine, compared with chloroquine-proguanil, or pyrimethamine-sulfadoxine prophylaxis, in the first trimester of pregnancy. Standard doses of quinine do not increase the risk of abortion or preterm delivery. Therapeutic mefloquine does not provoke hypoglycaemia. There is no evidence in the literature to support the hypothetical risk of kernicterus in the newborn, following exposure to antimalarial drugs containing sulphonamides or sulphones prior to delivery. Documentation of the safety of doxycycline, halofantrine, and the artemisinin derivatives in the treatment of malaria in pregnant women is currently limited.

CNS adverse events associated with antimalarial agents. Fact or fiction?

CNS adverse drug events are dramatic, and case reports have influenced clinical opinion on the use of antimalarials. Malaria also causes CNS symptoms, thus establishing causality is difficult. CNS events are associated with the quinoline and artemisinin derivatives. Chloroquine, once considered too toxic for humans, has been the antimalarial of choice for 40 years. While a range of serious CNS effects have been documented during chloroquine therapy, the incidence is unclear (extrapyramidal symptoms occur with an incidence of 1 in 5000). Amodiaquine has a higher incidence of mild CNS effects than chloroquine. Mefloquine therapy causes dose-related transient dizziness. Serious CNS events during mefloquine therapy occur in 1:1200 Asians and 1:200 Caucasians/Africans. Risk factors include dosage, concomitant drug use/interactions, previous history of a CNS event and disease severity. Retreatment (within a month) increases the risk in Asians 7-fold. Studies indicate that the frequency of serious CNS events with mefloquine prophylaxis (1:10,000) is similar to that with chloroquine (1:13,600). Quinine causes cinchonism at standard therapeutic doses. High-tone hearing loss occurs, but irreversible auditory or ocular effects are very rare. The artemisinin derivatives are associated with dose-dependent brain lesions in rodent, canine and nonhuman primates. At low doses, histological injury has been demonstrated, without clinical neurological signs. No significant toxicity has been reported in humans. Other antimalarial drugs are seldom associated with CNS adverse events. Data do not suggest a need to diminish the correct use of the quinoline derivatives. Irreversible effects are extremely rare and usually associated with overdosing or prior history of a serious CNS event. Concomitant therapeutic use of 2 drugs from the same family, or retreatment with the same drug, should be avoided. Onset of drug-associated serious CNS events requires drug discontinuation and future avoidance of the drug.

Validation of malaria surveillance case reports: implications for studies of malaria risk.

STUDY OBJECTIVE: The aim of the study was to investigate the quality of national malaria surveillance reports in the United Kingdom. DESIGN: Persons with malaria reported to the Malaria Reference Laboratory (MRL) in 1987 were contacted by post to verify existing records with respect to key variables. The MRL data set was then analysed for inaccuracies. SETTING: The study was confined to UK residents. PARTICIPANTS: 602 persons with malaria in 1987 responded (53%). MEASUREMENTS AND MAIN RESULTS: Review of case reports showed few missing data except for duration of residence in the UK, detailed chemoprophylactic regimens, and compliance. There were more missing surveillance data in reports of ethnic minority groups, principally in dates of travel (p = 0.008) and chemoprophylaxis use (p less than 0.0001). Patient recall in the survey was at variance with the surveillance reports in dates of travel and onset of infection, chemoprophylaxis use, and in compliance. Surveillance reports overestimated the number of days between leaving a malarious area and onset of symptoms (by 9 d for P falciparum and by 24 d for P vivax), and underestimated the delay between onset and diagnosis of P falciparum by 3 d. Over 50% of patients who had recalled the use of chloroquine, proguanil, pyrimethamine/dapsone, and pyrimethamine had not been recorded as having taken these drugs on the surveillance reports. Reported compliance also differed between the two data sets. CONCLUSIONS: It is recommended that research units test the quality of their surveillance data before embarking on analytical studies used to generate health policy guidelines.

Regulation of drug use and post-registration surveillance.

Artemisinin and its derivatives are already registered and available in some east Asian countries, and will soon become so in some countries in Africa. Regulatory mechanisms need to be strengthened in tropical countries to ensure the quality, safety and efficacy of these valuable drugs. Steps also need to be taken to improve dissemination of scientific information. A consensus has been reached internationally on the role of artemisinin and its derivatives in the current treatment of malaria, and guidelines drawn up. Post-registration surveillance is needed to monitor, at country level, drug efficacy, safety, and quality.

Epidemic dysentery in western Kenya.

This paper describes the epidemiology of a probable Shigella dysenteriae type 1 dysentery epidemic in western Kenya. A retrospective record review over 2 years of all cases of dysentery, amoebiasis and diarrhoea was carried out in 13 healthcare facilities in the Rarieda Division of Nyanza province. Of the 3301 cases recorded, 2191 were dysentery, giving a cumulative 2 years incidence rate for dysentery of 4%. The epidemic began in December 1994 and peaked in February 1995, coinciding with the very dry season. One location in the area had an overall attack rate of 9.3%, double that of other locations. Highest rates were in children aged < 5 years and in persons > 15 years old. S. dysenteriae type 1, with its increasing multiantibiotic resistance, is a continuing threat to the health of people in this region; this area may be suitable for intensive, prospective surveillance as a prelude to a Shigella vaccine trial.

Economic implications of resistance to antimalarial drugs.

The widespread evolution of drug resistance in malarial parasites has seriously hampered efforts to control this debilitating disease. Chloroquine, the mainstay of malaria treatment for many decades, is now proving largely ineffective in many parts of the world, particularly against the most severe form of malaria--falciparum. Alternative drugs have been developed, but they are frequently less safe and are all between 50 and 700% more expensive than chloroquine. Choice of drug clearly has important budgetary implications and national malaria control programmes need to weigh up the costs and benefits in deciding whether to change to more effective but more expensive drugs. The growth in drug resistance also has implications for the choice of diagnostic tool. Clinical diagnosis of malaria is relatively cheap, but less specific than some technological approaches. As more expensive drugs are employed, the cost of wasted treatment on suspected cases who do not in fact have malaria rises and the more worthwhile it becomes to invest in more specific diagnostic techniques. This paper presents an economic framework for analysing the various malaria drug and diagnostic tool options available. It discusses the nature of the key factors that need to be considered when making choices of malaria treatment (including treatment costs, drug resistance, the costs of treatment failure and compliance) and diagnosis (including diagnosis cost and accuracy, and the often overlooked costs associated with delayed treatment), and uses some simple equations to illustrate the impact of these on the relative cost effectiveness of the alternatives being considered. On the basis of some simplifying assumptions and illustrative calculations, it appears that in many countries more effective drugs and more specific and rapid diagnostic approaches will be worth adopting even although they imply additional expense.

Safety of mefloquine and other antimalarial agents in the first trimester of pregnancy.

BACKGROUND: Safe and effective antimalarials are required to protect pregnant women from the harmful effects of malaria. METHODS: Data were collected from two separate prospective cohorts to ascertain the safety of chloroquine-proguanil, sulfadoxine-pyrimethamine (SP), and mefloquine taken in the first trimester of pregnancy. RESULTS: In a traveler cohort of 236 pregnant women, spontaneous abortions were reported in 7.6% of 99 women taking chloroquine-proquanil, 0% of 19 taking sulfadoxine-pyrimethamine, and 9.1% of 118 women taking mefloquine. Anomalies were identified in 1.7%, 0% and 0% of the same cohort, respectively. Differences in rates of adverse outcomes between the three groups were not statistically significant. In a pharmaceutical database of 331 and 153 women exposed to mefloquine and SP, respectively, the overall rate of abnormal outcomes (spontaneous abortions plus fetal anomalies) was not significantly different (p=.29). Spontaneous abortions were significantly higher with mefloquine than SP (9.1% and 2.6%, respectively; p=.01), but the higher rate was comparable to background rates (7%-11%). Fetal anomalies in the mefloquine group (4.8%) were lower than the SP group (7.8%), but this was statistically not significant (p=.19), and was comparable with the background rate of 4.6% (p=.84). However, mefloquine exposure resulted in a significantly higher rate of therapeutically induced abortions, undertaken for perceived risk to the fetus, compared with SP (p<.0001). CONCLUSION: From the clinical data available, there is no indication that the risk of taking mefloquine in the first trimester of pregnancy is greater than that from any of the other antimalarials studied and the risk is considerably lower than that associated with falciparum malaria.

Efficacy of drug prophylaxis.

With the spread of chloroquine resistant Plasmodium falciparum the control of malaria has become increasingly complex. In recent years, particular concern has arisen over how best to prevent malaria in non-immune international travellers. Prior to the recognition of the potential toxicity of some antimalarial drugs, malaria preventive guidelines switched from chloroquine to the newer compound antimalarial drugs and to amodiaquine; this adjustment was made when sentinel cases alerted clinicians that breakthrough infections occurred in travellers to East Africa taking chloroquine prophylaxis. Changes were also supported by data derived from field studies illustrating the effectiveness of these drugs for therapy in indigenous populations. However, international studies have now documented serious adverse reactions to pyrimethamine/dapsone, pyrimethamine/sulphadoxine, and amodiaquine, and caution is required with their use. Rates in British users concur with international estimates. Specialists preparing malaria preventive guidelines have, therefore, preferred to recommend the use of relatively safe antimalarial drugs, like chloroquine and proguanil, provided they offer non-immune travellers adequate protection against P. falciparum infections. Substantial difficulty has arisen, however, in the definition of 'adequate protection'. Field studies in indigenous communities with partial immunity can provide concise biological measures of parasite resistance to drugs. Unfortunately, these data cannot be used directly to determine the expected efficacy of chemoprophylactic drugs in non-immune populations. The transmission of malaria and the degree and intensity of resistance vary even within small geographical areas. Comprehensive patterns of resistance cannot be mapped out on a countrywide or regional basis for logistic reasons, and are restricted focally to discrete study locations.(ABSTRACT TRUNCATED AT 250 WORDS)

Serious adverse drug reactions to pyrimethamine-sulphadoxine, pyrimethamine-dapsone and to amodiaquine in Britain.

All reports of adverse reactions with pyrimethamine-sulphadoxine (Fansidar), pyrimethamine-dapsone (Maloprim), and amodiaquine spontaneously reported through the UK national post-marketing system were reviewed. Retrospective reporting rates of serious reactions associated with these drugs were analysed using prescription data from the Department of Health, derived from the Prescription Pricing Authority, and relevant pharmaceutical companies. Whilst interpretation of these data requires caution, they allowed comparison with reporting rates from other studies. The reported rate for all serious reactions to pyrimethamine-sulphadoxine was 1:2100 prescriptions, and for cutaneous reactions was 1:4900 prescriptions, with a fatality rate of 1:11,100. The reported rate for serious reactions to pyrimethamine-dapsone was 1:9100 prescriptions, and for blood dyscrasias was 1:20,000 prescriptions, with a fatality rate of 1:75,000. The reported rate of blood dyscrasias associated with amodiaquine was 1:2100 users with a fatality rate of 1:31,000. Serious hepatic disorders occurred in 1:11 1000 pyrimethamine-sulphadoxine prescriptions, 1:75,200 pyrimethamine-dapsone prescriptions, and in 1:15,650 amodiaquine users. 35% of cases received these drugs needlessly as they were not exposed to drug resistant strains of Plasmodium falciparum. Since few serious reactions have been reported to chloroquine plus proguanil, these data support guidelines which restrict the use of reviewed drugs for those at greatest risk of infection. Dosage data indicated that fatalities had taken higher doses and continued prophylaxis after onset of symptoms. Two thirds of serious reactions to the compound antimalarials were reported in females.

Risk of malaria in British residents returning from malarious areas.

OBJECTIVES: To identify which British residents travelling abroad are at greatest risk of malaria infection, and to determine the efficacy of malaria chemoprophylaxis for preventing P falciparum infections in tropical Africa. DESIGN: Prospective cohort study (case-base linkage) with routine national surveillance systems. Denominators (base population) were obtained from monitoring a random sample of returning British travellers with the international passenger survey. Numerators (cases) were obtained from reports of malaria infections in British residents, through the Malaria Reference Laboratory network. SETTING: International passenger survey conducted at passport control of international airports in Britain. Malaria reports received nationally were collated centrally in London. SUBJECTS: 2948 British residents (0.2%) returning to Britain in 1987 randomly selected and questioned and 1052 British residents with microscopically confirmed malaria infections in 1987, whose case reports were reviewed and on whom additional data were collected by postal survey. MAIN OUTCOME MEASURES: Annual incidence subdivided by categories of risk. Chemoprophylactic efficacy for east and west Africa by principal regimens and compliance. RESULTS: Annual rates of reported infection per 100,000 travellers to Oceania were 4100; to west and east Africa were 375 and 172 respectively; to Latin America, the Far East, and the Middle East were 12, 2, and 1 respectively. Immigrants visiting friends and relatives in Ghana and Nigeria were at greatest risk (1303 and 952 per 100,000 respectively) in west Africa. Business travellers to Kenya experienced the highest attack rates in east Africa (465 per 100,000). Age-sex specific attack rates varied by region. No prophylaxis was reported to have been used by 23% of British visitors to west Africa, 17% to east Africa, 46% to central or southern Africa, and 58% visiting south Asia. The efficacy of chloroquine plus proguanil against P falciparum infection was 73% and 54% in west and east Africa respectively. Lower values were obtained for chloroquine alone and proguanil alone. The efficacy of Maloprim (pyrimethamine-dapsone) was 61% in west Africa, but only 9% in east Africa. Visitors to west Africa who did not comply with their chemoprophylactic regimen were at a 2.5-fold higher risk of infection than fully compliant users. Non-compliant visitors to east Africa had similar rates of infection as non-drug users. CONCLUSIONS: In 1987 chloroquine plus proguanil was the preferred chemoprophylactic regimen for P falciparum infection in Africa; antimalarial drugs must be taken regularly to be effective.

Epidemiological and control issues related to malaria in pregnancy.

Pregnant women infected with malarial parasites have an increased risk of maternal anaemia, abortion, stillbirth, prematurity, intra-uterine growth retardation, and infants of low birthweight. A 'state-of-the-art' symposium on malaria in pregnancy was convened in Kisumu, Kenya, in November 1997, to discuss the biological and clinical impact of malaria in pregnancy, and to identify antimalarial drugs and control strategies to protect pregnant women. The deleterious effects of malarial infection during pregnancy were shown to be associated both with Plasmodium falciparum and P. vivax infections, and to occur under a wide range of malaria transmission pressures. Control interventions, thus, need to be targeted at pregnant women in all endemic areas. Alternative antimalarial drugs to chloroquine have been tested and shown to be effective (and safe) against malaria in pregnancy. Delivery of cost-effective control interventions has been explored; investments are needed to facilitate the scaling-up of successful approaches to national-programme level. Several important research questions related to malaria in pregnancy were highlighted at the Kisumu meeting. Increased international and local commitment, to resource effective malaria control in pregnancy adequately, is a public-health priority.