Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial.

BACKGROUND: Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. METHODS: In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7-30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. RESULTS: Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2.5%vs 3.0%, p=0.1). Two versus 13 (0.03%vs 0.22%, p=0.0020) were permanently disabled; total dead or disabled: 156 versus 190 (2.6%vs 3.2%, p=0.0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 [1.6%] vs 82/4426 [1.9%], risk ratio 0.86 [95% CI 0.63-1.18], p=0.35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesunate significantly reduced death or permanent disability (29/1566 [1.9%] vs 57/1519 [3.8%], risk ratio 0.49 [95% CI 0.32-0.77], p=0.0013). INTERPRETATION: If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability. FUNDING: UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Foundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU).

Prevention of malaria using ITNs: potential for achieving the millennium development goals.

The use of insecticide treated nets is effective in reducing all cause malaria mortality and morbidity between 17 and 43% in children under five years and provides protection to pregnant women who are most susceptible to malaria. ITNs (Insecticide Treated Nets) are easy to use and require less technical and capital outlay to implement compared with other vector control methods. They are cost-effective, which has led to widespread implementation of ITNs by countries on a large scale. ITN use has however been limited due to the cost outlay households require to make towards the purchase of nets, households' inability to associate the effectiveness of the net with the insecticide leading to low re-treatment rates in most settings and the seasonality associated with the spread of malaria. This chapter provides a review of research on ITN, strategies of improving the availability and effectiveness of the nets and a comparison of ITNs and other malaria preventive methods. The review highlights inequity in ITN use among various socio-economic groups with the poorest being the least to benefit from ITNs even where they are highly subsidized. It discusses the break through in the production of PermaNet to resolve the problem of low re-treatment of nets.

Prevalence of Risk Factors for Non-Communicable Diseases for New Patients Reporting to Korle-Bu Teaching Hospital.

BACKGROUND: The risk factors of Noncommunicable diseases (NCDs) are not routinely monitored, especially among populace reporting to hospitals to detect and also advise on preventive measures, a key strategy to reducing the impact of NCDs on the Health Care System and population. METHODS: A cross-sectional survey was carried out between the months of May and June, 2010 among a sample representative of the medical and surgical out-patients population to determine the prevalence of certain risk factors of non-communicable diseases (NCDs). Participants (n = 230) were selected by systematic random sampling. Standardised international protocols were used to measure the prevalence of smoking, alcohol consumption, physical inactivity, obesity, raised blood pressure, raised blood glucose and total cholesterol. RESULTS: The obesity level of the study population was 40.4% with 54% being overweight. Tobacco use among the respondents was 4.8%. Alcohol consumption was 64.8%, with 54.3% of the study population being physically inactive. Almost 48%and 70.9% of the participants consumed fruits and vegetables respectively, at least three days in a week. The prevalence of hypertension was 33.6% for men and 35.2% for women. The prevalence of raised glucose and total blood cholesterol level among the study population was 6.5%. Almost 62% of the participants had a combination of three or more risk factors. CONCLUSION: The prevalence of the significant risk factors in this study were physical inactivity (54.3%), alcohol consumption (64.8%), overweight (54%), obesity (40.4%) and raised blood pressure (34.3%). Hospitals should therefore include NCD risk factor monitoring as part of routine services.

Vitamin A supplementation and childhood malaria in northern Ghana.

Two companion, randomized, placebo-controlled trials of prophylactic vitamin A supplementation provided the opportunity to assess the impact of supplementation on malaria parasitemia, morbidity, and mortality in young children in northern Ghana. In the mortality study, 21,906 children were visited every 4 mo over 2 y, and in the morbidity study 1455 children were visited weekly for 1 y. There was no difference between children supplemented with vitamin A and those given placebo in malaria mortality rates (rate ratio = 1.03; 95% CI 0.74, 1.43) or fever incidence based on reported symptoms. Malaria parasitemia rates, parasite densities in children with a positive blood smear, and rates of probable malaria illness also did not differ between treatment groups. There was no correlation between serum retinol at the beginning of the trial and subsequent malaria parasitemia in children who received placebo (r = 0.01). It is concluded that vitamin A supplementation had no impact on malaria in this population.

Effect of vitamin A supplementation on the growth of young children in northern Ghana.

The effect of prophylactic vitamin A supplementation on child growth was studies in two randomized, placebo-controlled trials carried out in adjacent areas of northern Ghana between 1989 and 1991. In the Health Study, the midupper arm circumference (MUAC) and weight of the approximately 1500 children (aged 6-59 mo) in the trial were measured every 4 wk for up to 52 wk. In addition, MUAC, weight, and height were measured at each of the four potential vitamin A or placebo dosing times, which were at 4-mo intervals. In the Survival Study, MUAC and weight were measured at 4-mo intervals at each of seven dosing rounds in the approximately 15 000 children currently in the trial. Overall, there were > 90 000 observations of weight and MUAC in > 25 000 children, and 3347 observations of length/height in 1546 children. Within each study, the mean monthly weight, MUAC, and gains in length/height in each treatment group were compared by using multilevel modeling. There were no significant differences in either MUAC or gains in length/height. The only significant difference in weight gain was in the Survival Study: children in the vitamin A-supplemented group who were > or = 36 mo of age had a mean weight gain that was 3 g lower per month (95% CI: 0.4, 5.0, P = 0.02) than that in the placebo group; a difference that was unlikely to be functionally important in this age group. Vitamin A supplementation did not lead to any increased growth in this population of young children, in whom supplementation reduced mortality and severe morbidity substantially.

Measurement of the frequency and severity of childhood acute respiratory infections through household surveys in northern Ghana.

BACKGROUND: Methodological issues in the design and interpretation of cross-sectional interview surveys of the prevalence of acute respiratory infections (ARI) were assessed among young children. METHODS: A cross-sectional survey was conducted in approximately 20,000 children in the north of Ghana. Approximately half were administered a questionnaire in which the initial questions about recent illnesses were direct questions about the presence or absence of three specific ARI-related symptoms (cough, rapid breathing, difficulty breathing), while the other half were administered a questionnaire which started with an open-ended question on whether the child was ill, designed to elicit spontaneous responses. A 2-week recall period was used in addition to point prevalence questions for half of the children in each group, while 4 weeks was used for the other half. The results were compared with those from a longitudinal morbidity surveillance system in an adjacent population of children. The repeatability of the responses to each of the symptoms/conditions was assessed in a subsample of the children. RESULTS AND CONCLUSIONS: The point and period prevalence rates of ARI symptoms or conditions based on spontaneously elicited responses were more likely to be valid than those based on prompted responses. Furthermore, using a 2-week recall period appeared to give more valid period prevalence rates than a 4-week recall period. The repeatability of the various ARI questions was not high (kappas 0.14 to 0.49), irrespective of the questionnaire design. Whether these findings will also be true in other populations needs to be assessed.

Survival and sequelae of meningococcal meningitis in Ghana.

BACKGROUND: Meningococcal meningitis epidemics are frequent in the Sahel zone of Africa but there is little information on the frequency of long-term sequelae. We analysed excess mortality in the two years following the 1997 epidemic in northern Ghana and carried out a case-control study to assess sequelae in the survivors. METHODS: Two-year survival of 696 meningitis cases recorded at the War Memorial Hospital, Navrongo, was analysed using data from a demographic surveillance system. A structured questionnaire on disability and on psychiatric, neuropsychological and behavioural problems was administered to 505 of the survivors and 505 age- sex- and location-matched controls as well as to their respective relatives. Cases and controls underwent full neurological and neuropsychological examination and were evaluated for hearing impairment by audiometry. RESULTS: Survival rates after the first month following the attack were similar in cases and controls. Hearing impairment was the major sequela, and was reported in 6 per cent of cases and 2 per cent of controls (odds ratio [OR] = 3.10; 95% CI : 1.48-7.09). Audiometry detected severe and profound hearing loss in the worse affected ear (> or =70 db) in 8/496 (1.6%) survivors but in only one control. Survivors of meningitis were more likely to suffer from feelings of tiredness (OR = 1.47; 95% CI : 1.03-2.11) and were more often reported by relatives to have insomnia (OR = 2.31; 95% CI : 1.17-4.82) and daily alcohol consumption. INTERPRETATION: Meningococcal meningitis annually causes approximately 10 000 cases of deafness in sub-Saharan Africa; there is a need for early detection of affected survivors and promotion of simple hearing devices. There is a sizeable burden of depressive disorders secondary to meningitis which should be identified and looked after appropriately.

Risk factors for child mortality in northern Ghana: a case-control study.

BACKGROUND: A population-based case-control study was carried out to investigate potential risk factors for post-neonatal and child mortality in northern Ghana were child survival rates are among the lowest in Africa. METHOD: Cases were post-neonatal infant and child deaths identified within a large population under continuous demographic surveillance. For each case, one living control, matched for age, sex and locality, was selected from the demographic database. Mothers of each case and control were interviewed to obtain information on social, enconomic, demographic, environmental and other possible risk factors. Matched analyses of the 317 cases and their controls were performed using discordant pairs analysis and conditional logistic regression. RESULTS: The mortality rate for children aged 6 months to 4 years was estimated as 23.9/1000 children/year. An increased risk of death was observed where the delivery was not performed by a trained person (OR = 1.8, 95% CI: 1.0-3.2), if the preceding birth interval was < 24 months (OR = 2.2, 95% CI: 1.1-3.9), if the father beat the child's mother (OR = 4.3, 95% CI: 1.2-15.6) or if the water source was unprotected (OR = 1.6, 95% CI: 1.0-2.7). No association was found between weaning practices, parental education, or any of the socioeconomic or hygiene variables considered. CONCLUSIONS: Few strong risk factors for mortality were identified, perhaps because living conditions within the study population are relatively homogeneous. While mortality rates may be reduced by targeted interventions, such as increasing deliveries by trained people, more general improvements in the socioeconomic status in the region are essential.

PIP: A population-based case-control study was conducted in the Kassena-Nankana district of the Upper East Region of Ghana to investigate potential risk factors for post-neonatal and child mortality in northern Ghana where child survival rates are among the lowest in Africa. 317 cases of post-neonatal infant and child deaths were matched with controls, with matched analyzes subsequently conducted using discordant pairs analysis and conditional logistic regression. Mothers of each case and control were interviewed to obtain information on social, economic, demographic, environmental, and other possible risk factors. The mortality rate for children aged six months to four years was estimated as 23.9/1000 children/year. An increased risk of death was observed where the delivery was not performed by a trained person, if the preceding birth interval was less than 24 months, if the father beat the child's mother, or if the water source was unprotected. No association was found between weaning practices, parental education, or any of the socioeconomic or hygiene variables considered. The authors note that few strong risk factors for mortality were identified possibly due to the relatively homogeneous living conditions within the study area. While mortality rates can be reduced by targeted interventions, general improvement in the socioeconomic status in the region is needed.

Toward a framework and indicators for monitoring Roll Back Malaria.

Roll Back Malaria (RBM) is a new global partnership that aims to halve the malaria burden by the year 2010. A framework and indicators for monitoring the outcomes and impact of RBM have been defined through an extensive consultative process. The framework identifies critical areas for monitoring RBM action relating to 1) the impact on malaria burden, 2) improvements in malaria prevention and treatment, 3) related health sector development, and 4) support for RBM action (including partnerships). A set of RBM indicators has been defined that corresponds to these critical areas but that reflects the major variations in malaria epidemiology and the principal interventions in different parts of the world. Countries would select indicators that are appropriate for their situation. Four global indicators are proposed for use by all countries in which RBM action is under way. Data collection procedures are discussed, and it is indicated how monitoring RBM action can build on existing data-collection mechanisms.

Impact of spatial distribution of permethrin-impregnated bed nets on child mortality in rural northern Ghana.

Effects of the distribution in space of permethrin (insecticide)-impregnated bed nets (IIBNS) on child mortality were studied in a randomized controlled trial of IIBNs in a an area highly endemic for Plasmodium falciparum malaria in rural northern Ghana. Eight hundred sixty-two deaths occurred among children 6-59 months of age during 16,841 child-years-at-risk. Mortality increased with the distance from health facilities but not with proximity to identifiable anopheline breeding sites (reservoirs). The efficacy of IIBNs was independent of these distances. Mortality in users of IIBNs was independent of the proximity of nonusers, and mortality rates of nonusers and users living close to each other were similar. Poisson regression estimated a 6.7% increase in mortality among nonusers with each 100-m shift away from the nearest compound with IIBNS, indicating that the insecticide protects nearby nonusers. High coverage of IIBNs achieves maximum impact, but users of IIBNs offer some protection to less fortunate neighbors if coverage is incomplete.

Severe anemia in young children after high and low malaria transmission seasons in the Kassena-Nankana district of northern Ghana.

Malaria and anemia accounted for 41% and 18% respectively of hospital deaths in the Kassena-Nankana district of northern Ghana during 1996. We measured hemoglobin (Hb), malaria prevalence, and anthropometric indices of 6--24-month-old infants and young children randomly selected from this community at the end of the high (May-October, n = 347) and low (November-April, n = 286) malaria transmission seasons. High transmission season is characterized by rainfall (the equivalent of 800-900 mm/yr.), while the remaining months receive less than 50 mm/yr. Severe anemia, defined as Hb < 6.0 g/dL, was 22.1% at the end of the high transmission season compared to 1.4% at the end of the low transmission season (Odds Ratio [OR] = 20.1; 95% CI: 7.1-55.3). Parasitemia was 71% and 54.3% at these time points (OR = 2.1; 95% CI: 1.5-2.9). Nutritional anemia appeared to have little impact upon this seasonal difference since anthropometric indices were comparable. Although the relative contributions of other causes of severe anemia were not assessed, repeated malaria infections may be a primary determinant of severe anemia among infants and young children during the high transmission season.

Incidence of symptomatic and asymptomatic Plasmodium falciparum infection following curative therapy in adult residents of northern Ghana.

Adult residents of holoendemic malaria regions in Africa have a naturally acquired immunity (NAI) to malaria that renders them more resistant to new infections, limits parasitemia, and reduces the frequency and severity of illness. Given such attributes, it is not clear how one might evaluate drug or vaccine efficacy in adults without serious confounding. To determine symptomatic and asymptomatic malaria attack rates in adults of northern Ghana, 197 men and women underwent curative therapy for any pre-existing malaria infections at the start of the high transmission (wet) season. They were monitored for first parasitemia and first clinical episode of infection by Plasmodium falciparum over a 20-week period (May-October 1996). The cumulative incidence of primary infection by P. falciparum was 0.98 and incidence density of infection was calculated to be 7.0 cases/person-year. Symptoms were reported by 19.5% of the individuals at the time of first recurrent parasitemia. Incidence of infection, parasite density, and the frequency of symptoms were comparable in males and females. The results suggest that NAI did not provide these adults with significant defense against rapid re-infection and suggest that this population-infection design could serve to demonstrate the efficacy of a drug or vaccine in preventing parasitemia.

Parasitological and clinical aspects of bancroftian filariasis in Kassena-Nankana District, upper east region, Ghana.

A survey of the prevalence of bancroftian filariasis was conducted in August-September 1992 in the northern part of the Kassena-Nankana District, Upper East Region, Ghana. 200 compounds from 3 different communities were randomly selected from the vitamin A trial database. All resident compound members were examined for clinical manifestations of lymphatic filariasis and capillary blood was obtained between 21:00 and 01:00 and examined using the counting chamber technique. 1603 people were examined, 741 males and 862 females. The overall prevalence of microfilaraemia was 32.4% (95% confidence interval 30.1-34.7). Geometric mean microfilaria density (infected persons only) was 794 per mL. The most important clinical manifestation was hydrocele (in 32% of males) followed by limb elephantiasis (in 3.6% of the study population). There was no significant difference between the 3 communities in clinical or parasitological findings.

Mortality in a seven-and-a-half-year follow-up of a trial of insecticide-treated mosquito nets in Ghana.

A 17% efficacy in preventing all-cause mortality in children aged 6-59 months was previously reported from a cluster-randomized controlled trial of insecticide-treated mosquito nets (ITNs) carried out in the Kassena-Nankana District of northern Ghana from July 1993-June 1995. A follow-up until the end of 2000 found no indication in any age group of increased mortality in the ITN group after the end of the randomized intervention. These results should further encourage the use of ITNs as a malaria control tool in areas of high endemicity of Plasmodium falciparum.

Lay reporting of elephantiasis of the leg in northern Ghana.

Within a large scale community trial in northern Ghana lay interviewers were trained to inquire about and identify elephantiasis of the leg by the use of local terms and simple examination of respondents. This was repeated a year later after moving the interviewers to different geographical areas. The proportions of extended family compounds reported to have at least one member with elephantiasis of the leg were 12.2% and 12.1 % respectively in the first and second surveys (kappa = 0.60). 'Blind' re-examination of a sub-sample by a physician showed a high level of agreement with the lay interviewer's findings in the first and second surveys (kappa = 0.67 and 0.82 respectively). This study has shown that lay people, even with minimal training, can obtain repeatable and valid estimates of the prevalence of elephantiasis of the leg, at least within an area where local terms for the condition are available. This method could potentially be used for other diseases with visible manifestations.

Patterns of malaria morbidity and mortality in children in northern Ghana.

A malaria prevalence survey was carried out in young children in northern Ghana between October 1990 and September 1991, in an area with continuous mortality and morbidity surveillance. There was marked seasonal variation in malaria deaths, reported fevers, parasite rates and mean parasite densities, with parasite rates reaching 85-94% in the wet season. The monthly numbers of malaria deaths were highly correlated with rainfall in the previous 2 months (r = 0.90, P < 0.001). Parasite rates were highest in the oldest children (5-7 years), but parasite densities and rates of febrile illness were highest in those 6-11 months old. Haemoglobin levels were also at their lowest in this age group. The predominant species, Plasmodium falciparum, was present in 71% of all blood films. Febrile illness was well recognized by mothers, but it was not possible to construct a simple clinical diagnostic algorithm which would identify even 50% of children with high levels of malaria parasitaemia (> or = 4000 parasites/microL). Malariometric indicators appear to have changed little in this area since a previous survey in 1955.

Risk factors for meningococcal meningitis in northern Ghana.

Meningococcal meningitis is a major cause of morbidity and mortality in the meningitis belt of sub-Saharan Africa where it occurs in epidemics every 8-12 years. Risk factors for the disease in this setting remain largely unknown. We carried out a case-control study to investigate possible risk factors among survivors of a meningitis epidemic occurring in 1997 in northern Ghana. A structured questionnaire on socio-economic factors, housing and household overcrowding, smoking and exposure to smoke and close contact with a case was administered to 505 of the survivors and 505 of age-, sex- and location-matched controls. Cooking in kitchens with firewood stoves (OR 9.00, CI 1.25-395) and sharing a bedroom with a case (OR 2.18 CI 1.43-3.4) were found to be risk factors for disease. Socio-economic factors, overcrowding, smoking and passive exposure to tobacco smoke were not found to be risk factors. Exposure to smoke from cooking fires or close contact with a case puts people at risk of contracting meningococcal meningitis. In the hot dry months, exposure to smoke from cooking fires should be minimized by encouraging alternatives to cooking over wood fires, or cooking outside. If wood-burning stoves cannot be avoided, kitchens should be made larger with improved ventilation. Meningitis cases should be nursed in well-ventilated rooms and the number of people sharing a room with a case kept at a minimum.

Cultural factors constraining the introduction of family planning among the Kassena-Nankana of northern Ghana.

This study presents a focus group investigation of reasons why women in a rural, Sahelian community are reluctant to adopt family planning even when convenient services are made freely available. First, women opting to practice contraception must do so at considerable risk of social ostracism or familial conflict. Implementing individual preference is something that must be done without the support of others. Second, few women view personal decisions about contraceptives as theirs to make. Women and children are the property of the corporate family-kin and community militate against reproductive control. Third, although children are highly valued for a variety of economic, social, and cultural reasons, mortality risks remain extremely high. Low fertility imposes the unacceptable risk that a woman will have no surviving children at the end of her reproductive life. Taken together, these findings attest to the inadequacy of service strategies focused on the contribution of distribution, individual agency, or personal choice. Outreach should also build a sense of community legitimacy for the program, collective health action, and traditional leadership support for family planning behavior.

The cost-effectiveness of permethrin impregnated bednets in preventing child mortality in Kassena-Nankana district of Northern Ghana.

Permethrin impregnated bednets are now being widely promoted as an effective means of protecting African children against malaria, but there is little evidence of their cost-effectiveness. The impact on child mortality of introducing permethrin impregnated bednets was evaluated in a rural district of northern Ghana in a controlled trial. The cost-effectiveness of the intervention is reported in this paper. The total cost of the intervention over the 2 years of follow-up was US $148,245. Cost per impregnated bednet per year and per person protected per year was US $2.4 and 1.2, respectively. Approximately 16,800 child years were protected and 74 child deaths averted at an estimated cost of US $8.8 per child year protected and US $2003 per death averted. In this rural community, where life expectancy at the mean age of death of trial children was 57.5 years, the estimated cost per discounted healthy life-year gained was US $73.5. Sensitivity analysis suggested that this cost-effectiveness ratio might be reduced substantially by feasible changes in programme implementation. This study supports the argument that the cost-effectiveness of bednet impregnation is sufficiently attractive to make it part of a package of high priority interventions for children. Issues of how to finance the provision of nets and insecticide, and especially the relative contribution of governments, households and donors, need urgently to be addressed.

Impact of primary health care on child morbidity and mortality in rural Ghana: the Gomoa experience [corrected].

The impact of a combination of PHC intervention activities on child survival, growth, morbidity and mortality was assessed in three selected rural communities (Gomoa Fetteh, Gomoa Onyadze/Otsew Jukwa and Gomoa Mprumem) in the Central Region of Ghana from 1987 to 1990. EPI, provision of basic essential drugs and supplies for the treatment of common childhood diseases, treatment of the sick child, growth monitoring, health education, provision of antenatal services, family planning, training and supervision of Community Health Workers, disease surveillance and special studies were the major PHC strategies used to improve the health of the child and the pregnant woman in the three communities. These activities in their totality have had significant impact on morbidity and mortality in children under five and on maternal mortality in children under five and on maternal mortality over the study period 1987 to 1990. Although malaria, acute respiratory infections and diarrhoea diseases continue to be major causes of childhood morbidity, deaths due to these diseases have dramatically declined. Measles and other vaccine preventable diseases no longer contribute significantly to childhood morbidity and mortality. Infant and under five mortality have been reduced from 114.6/1000 and 155.6/1000 live births to 40.8/1000 and 61.2/1000 live births respectively. The crude birth rates however, remain almost the same over the five year period (43 to 48/1000 pop.) but crude death rates have declined (11 to 12.4/1000 pop.).(ABSTRACT TRUNCATED AT 250 WORDS)