Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

Unsweetened natural cocoa has anti-asthmatic potential.

Unsweetened natural cocoa powder is enriched with nutraceutical abundance of anti-asthmatic compounds theobromine and theophylline. Cocoa powder, which is prepared after removal of the cocoa butter, contains about 1.9% theobromine and 0.21% caffeine. Anecdotal reports indicate that regular consumption of unsweetened natural cocoa powder (UNCP), a common practice in Ghana, West Africa, has the potential to reduce the tendency of asthmatic episodes. In the present paper we studied the effect of regular ingestion of aqueous extract of UNCP on hematological and histopathological changes that occur in ovalbumin (OVA)-sensitized guinea pigs. OVA-sensitized guinea pigs were challenged with aerosolized OVA 1 hour after ingestion of 300 mg/kg (low dose) or 600 mg/kg (high dose) of UNCP for 35 consecutive days. Histopathological and haematological changes in the OVA-sensitized guinea pigs were evaluated. Both negative and positive controls with distilled water and prednisolone, respectively, were used. OVA-sensitized guinea pigs demonstrated concentration-independent reduction in immune response to aerosolized OVA. There were no histo-architectural changes in the bronchiolar smooth muscles of the treated groups. Unsweetened natural cocoa powder has potential anti-asthmatic properties when administered orally at the doses tested.

Prostate-specific targeting of the aqueous root extract of Croton membranaceus in experimental animals.

Croton membranaceus Müll.Arg. (Euphorbiaceae) is used for benign prostate hyperplasia (BPH) treatment. The study aimed at investigating organs that the aqueous root extracts of C. membranaceus (CMARE) target, which is absent in literature. Twenty-four male Sprague-Dawley rats (100-140 g) were randomly divided into 4 groups. Group 1, the control group received distilled water. Groups 2, 3 and 4 received 30, 150 and 300 mg kg(-1) b.wt CMARE respectively (oral gavage). Rats fed 90 days the standard chow diet ad libitum. Upon sacrifice, major organs were histologically examined and serum prostate-specific antigen (PSA) biochemically determined. Only the prostate was abnormal. Histologically, H&E staining revealed thickness and infoldings of the epithelial cells shrinking with increasing dose. The 30 mg kg(-1) group showed low columnar or flattened epithelium cells, whereas the columnar epithelium infoldings of the 150 mg kg(-1) b.wt and 300 mg kg(-1) b.wt groups were virtually nonexistent. The acini of the control, 30 mg kg(-1) b.wt group and the 150 mg kg(-1) b.wt groups showed clear pinkish secretion. However, secretion of the high-dose group appeared light pink in colour and the stroma cells appeared much darker than all the treated and control group. C. membranaceus targets the prostate with significant PSA reduction (P < 0.01).

Genotoxicity, cytotoxicity and toxicological evaluation of whole plant extracts of the medicinal plant Phyllanthus niruri (Phyllanthaceae).

Phyllanthus niruri is a medicinal plant (commonly known as stone breaker) found in the tropics and other parts of the world. It is known for its capacity to block the formation of calcium oxalate crystals and kidney stone formation in urolithiasis. This plant has been used to treat hyperglycemia, hypertension, pain, and mild cases of malaria. We examined the geno-, cyto- and overall toxicity of P. niruri whole plant ethanolic extract. The extract was administered as a single dose of 30 or 300 mg/kg to laboratory rats by gavage, accompanied by negative (0.9% saline) and positive (10 mg/mL N-ethyl-N-nitrosourea) controls that were injected intramuscularly 48 h after extract administration. The ratio of polychromatic (PCE)/normochromatic erythrocytes (NCE) from femur bone marrow was scored for genotoxicity. Cytotoxicity was determined using descending concentrations (0.2-0.0125 g/mL) of the extract incubated with peripheral blood mononuclear cells. Lactate dehydrogenase release from damaged cells was determined and the CC(50) calculated. Subchronic administration of the extract at 30 or 300 mg/kg was done for 90 days to determine general toxicity. PCE:NCE (%) for the extract and negative control was 63, compared to 168 (positive control). The CC(50) was 26.3 mg/mL and hepato-renal toxicity after subchronic extract administration was nil. We conclude that ethanol extract of P. niruri is not cytotoxic or genotoxic, and is generally non-toxic on subchronic administration.

Multiplex PCR and Microarray for Detection of Swine Respiratory Pathogens.

Porcine respiratory disease complex (PRDC) is one of the most important health concerns for pig producers and can involve multiple viral and bacterial pathogens. No simple, single-reaction diagnostic test currently exists for the simultaneous detection of major pathogens commonly associated with PRDC. Furthermore, the detection of most of the bacterial pathogens implicated in PRDC currently requires time-consuming culture-based methods that can take several days to obtain results. In this study, a novel prototype automated microarray that integrates and automates all steps of post-PCR microarray processing for the simultaneous detection and typing of eight bacteria and viruses commonly associated with PRDC is described along with associated multiplex reverse transcriptase PCR. The user-friendly assay detected and differentiated between four viruses [porcine reproductive and respiratory syndrome virus (PRRSV), influenza A virus, porcine circovirus type 2, porcine respiratory corona virus], four bacteria (Mycoplasma hyopneumoniae, Pasteurella multocida, Salmonella enterica serovar Choleraesuis, Streptococcus suis), and further differentiated between type 1 and type 2 PRRSV as well as toxigenic and non-toxigenic P. multocida. The assay accurately identified and typed a panel of 34 strains representing the eight targeted pathogens and was negative when tested with 34 relevant and/or closely related non-target bacterial and viral species. All targets were also identified singly or in combination in a panel of clinical lung samples and/or experimentally inoculated biological material.

Laminar and spatial localization of the islands of Calleja in mice.

The islands of Calleja (IC) are dense clusters of cells localized within the ventral striatum. The IC have been described as variable in both number and localization from animal-to-animal, however, a quantitative investigation of this variability is unavailable. Further, it is presently unknown whether the IC occupy select areas of the olfactory tubercle (OT), the ventral striatum structure which possesses the IC in mice. To address these questions, we examined the IC of adult C57bl/6 mice. As previously noted, we found substantial inter-hemispheric and inter-mouse variations in the total number of IC. While the IC were observed in all three cell layers of the OT, the bulk of IC occupied layer iii. The span of the IC along the anterior-posterior and medial-lateral axes of the OT was variant. Further, localizations of the IC within the OT also differed across animals. Notably, the probability of observing an IC in the medial OT was greater than that of observing one in the lateral. These data provide a fundamental characterization of both differences and similarities regarding the IC in mice and will be informative for future in vivo studies seeking to perturb and possibly record from the IC. Further, we predict that inter-animal diversity in the IC may be a mechanism for inter-animal differences in behavior, especially reward-related and motivational behaviors.

The effect of recall on estimation of incidence rates for injury in Ghana.

BACKGROUND: Injury is a major public health problem in many developing countries. Due to limitations of vital registry and health service data, surveys are an important tool to obtain information about injury in these countries. The value of such surveys can be limited by incomplete recall. The most appropriate recall period to use in surveys on injury in developing countries has not been well addressed. METHODS: A household survey of injury in Ghana was conducted. Estimated annual non-fatal injury incidence rates were calculated for 12 recall periods (1-12 months prior to the interview, with each successively longer period including the preceding shorter periods). RESULTS: There was a notable decline in the estimated rate from 27.6 per 100 per year for a one-month recall period to 7.6 per 100 per year for a 12-month recall period (72% decline). The extent of this decline was not influenced by age, gender, rural versus urban location, nor by type of respondent (in-person versus proxy). Rate of decline was influenced by severity of injury. Injuries resulting in <7 days of disability showed an 86% decline in estimated rates from a one-month to a 12-month recall period, whereas injuries resulting in > or =30 days of disability showed minimal decline. CONCLUSIONS: In this setting, longer recall periods significantly underestimate the injury rate compared to shorter recall periods. Shorter recall periods (1-3 months) should be used when calculating the overall non-fatal injury incidence rate. However, longer recall periods (12 months) may be safely used to obtain information on the more severe, but less frequent, injuries.

The epidemiology of acute adenolymphangitis due to lymphatic filariasis in northern Ghana.

A study to investigate the socioeconomic impact of lymphatic filariasis was conducted in a rural community in northern Ghana. The incidence, severity, and duration of acute adenolymphangitis (ADL), as identified by local terminologies and confirmed using World Health Organization diagnostic criteria, were investigated. Local terminologies were found to be highly specific and sensitive for diagnosing ADL (sensitivity = 0.978, specificity = 0.980). The incidence of ADL was 95.9 per 1,000 per annum among adults more than 10 years of age, being much higher in females than in males. Among those with elephantiasis and other chronic filarial symptoms, there was no clear relationship between the stage of chronic lymphedema and the incidence of ADL. The incidence of ADL was found to be closely related to the rainfall pattern. The design of the study, its findings, and the public health implications of the findings are discussed in this paper.

Descriptive epidemiology of lymphatic filariasis in Ghana.

A national filariasis survey was conducted to determine the prevalence and distribution of Wuchereria bancrofti microfilaraemia and clinical disease associated with lymphatic filariasis in Ghana. Multi-stage systematic sampling was used to select households to be examined in all 10 administrative regions of the country. The results showed a high prevalence of microfilaraemia and disease with considerable regional variation in all the quantities investigated. In general, the disease was more prevalent in the northern guinea savannah and the southern coastal savannah, while the middle forest belt was relatively free. Even within the regions, there was considerable variation in the distribution of the disease. The disease is of potentially major public health significance, particularly in the northern and coastal savannahs, and requires the design and implementation of a control programme.

Predicting the impact of school-based treatment for urinary schistosomiasis given by the Ghana Partnership for Child Development.

Mathematical models can be used to predict the impact of interventions to control infectious diseases. In this paper, an epidemiological model is used to predict the impact of chemotherapy of school-age children infected with Schistosoma haematobium, in a programme conducted by the Ghana Partnership for Child Development in the Volta Region, Ghana. Existing data were used to validate the predictions of the model, demonstrating convincingly the ability of the model to make correct predictions. Predictions of trends in mean egg count, infection prevalence and prevalence of heavy infection (> 50 eggs/10 mL urine) were then made for the period 1997-1999, and will be compared to the data collected in the programme in the future.

Alternatives to bodyweight for estimating the dose of praziquantel needed to treat schistosomiasis.

Data on age, height and mid upper-arm circumference (MUAC) from nearly 6000 schoolchildren in Ghana, Tanzania and Malawi (not MUAC) were used to examine their power to predict bodyweight and thus the dosage of praziquantel required to treat schistosomiasis. Height was found to provide a simple and reasonably accurate estimate of weight, and about 75% of children would have been given a dosage of praziquantel within the range normally given using bodyweight at a dosage of 40 mg/kg bodyweight. The upper and lower ranges in dosage did not exceed dosages of praziquantel which have been used before or are currently recommended to treat schistosomiasis. A pole marked with the number of tablets could thus be used as a simple way to determine the dose of praziquantel to treat children in school-based health programmes.

Rapid community diagnosis of lymphatic filariasis.

We conducted a pilot study to test rapid assessment procedures for the community diagnosis of lymphatic filariasis in some rural communities in Ghana. The assessment criteria included direct key informant interviews, focus group discussions, routine reporting from health facilities, self-administered questionnaires, and a random examination of adult males for hydroceles. All the data collection methods were easy, convenient, non-invasive to use and acceptable to the community. The study provided reliable estimates of the burden of lymphatic filariasis in the community when compared with data from standard epidemiological surveys. The direct key informant interviews and focus group discussions gave a broad perspective of the burden of diseases in the community in general, and lymphatic filariasis in particular. The use of self-administered questionnaires provided data comparable with data on elephantiasis in the community from a case search. Examination of a random 30-40 adult males for hydroceles provided a good correlation with the community microfilaria prevalence, with a correlation coefficient of linear regression r = 0.79. These individual rapid assessment procedures of the burden of lymphatic filariasis, if further developed and tested could, be widely used in combination for the mapping of the distribution of lymphatic filariasis in Ghana and possibly, the African sub-region.

Filariasis in northern Ghana: some cultural beliefs and practices and their implications for disease control.

This article reports on how some endemic rural communities in northern Ghana perceive and manage lymphatic filariasis. The disease was mainly attributed to supernatural and spiritual factors. Except for a few instances of neglect, the community was generally caring towards people with the disease. Issues related to marriage, stigma, concealment and leadership are discussed. On the whole, the importance of social and cultural perceptions of a disease and its relevance to control cannot be over emphasized.

Validity of women's self-reported obstetric complications in rural Ghana.

This retrospective study assessed the utility of women's self-reports to identify obstetric complications in rural Ghana. All consenting obstetric and postpartum inpatients, presenting from the seventh month of gestation to 42 days postpartum, were interviewed at the Holy Family Hospital, Techiman and were asked about their signs and symptoms. A combination of clinical examination and laboratory testing of urine and blood samples was used for determining case status. Self-reported obstetric complications of 340 women were compared with the corresponding diagnostic status for their sensitivity, specificity, predictive value, and test-efficiency. Using algorithms that could not be practically applied at the community level, self-reported symptoms correctly identified the majority (75%) of complicated and uncomplicated pregnancies, but missed one-quarter of cases requiring emergency obstetric care. The positive predictive value of 50% indicates that women's self-reported symptoms should not be used in estimating the incidence of these conditions or in identifying women requiring referral in this population.

Effect of vitamin E, low dose irradiation, and display time on the quality of pork.

A 4×2×3 factorial experiment was designed to investigate the effect of supplemental vitamin E (0, 100, 200, and 300 mg/kg feed), irradiation and days in display on quality characteristics of aerobically packaged ground pork and vacuum packaged loin chops. Color, thiobarbituric acid reactive substances (TBARS), olfactory and sensory characteristics were evaluated. Samples held in display for 3 d were used for sensory evaluation. In the ground pork, irradiation (1.9 kGy) increased "wetdog" flavor, increased a(*) (redness) and decreased L(*) (lightness) and b(*) (yellowness) values but had no effect on TBARS. However, as display time (0, 4, and 8 days) increased; the differences in a(*) values diminished and putrefying and fishy odors were higher in non-irradiated samples than irradiated. Supplemented vitamin E had no effect on TBARS, odor, and color measures; but increased the juiciness of ground pork regardless of irradiation. Similarly, in the loin chops, irradiation (1.5 kGy) increased a(*) value and "wetdog" flavor; but decreased b(*) value regardless of vitamin E supplementation. Also, irradiation reduced putrefying, and fishy odors during longer display times. TBARS increased with increased display time but was not affected by vitamin E supplementation. These results indicate that in aerobically packaged ground pork and vacuum packaged loin chops, radiolytic odors and color changes cannot be mediated with vitamin E supplementation. Display time and irradiation are significant in determining color and odor changes.

Continuous quality improvement in public health in Ghana: CQI as a model for primary health care management and delivery.

This article describes the context and examines factors influencing the quality of primary health care delivery and management in Ghana, West Africa. It describes the potential of continuous quality improvement as a management philosophy and tool to improve the quality of primary health care delivery and management in Ghana. It compares the Ghanaian context in which the use of continuous quality improvement in health care is new and untried with the developed country context (mainly the U.S.), where continuous quality improvement has a relatively long history of use in health care and is a requirement for the accreditation of health institutions. Finally, the article discusses the steps that have to be taken to translate continuous quality improvement from a theoretical management concept to improve quality of care to an actual managerial intervention in Ghana. In conclusion, continuous quality improvement is shown to be a potential viable approach to improving quality of care in the Ghanaian context and merits further investigation.

Computerised tomographic scan of the head in evaluation of stroke in Ghanaians.

One thousand and three patients clinically diagnosed as stroke cases were investigated using computerised tomographic (CT) scan. No diagnosis was made in 56 (5.58%) of the patients. While 56 cases had the CT scans reported as normal, in 40 (4.99%) of the patients disorders other than stroke were diagnosed. They included remediable causes like subdural haematoma (ten cases), cerebral abscess (eight cases), meningioma (four cases), other brain tumours (eighteen cases). Nine hundred and seven of the patients were proven to have suffered a stroke; 547 (60.3%) were haemorrhagic and 360 (39.7%) were infarctive. These results are at variance with previous studies from West Africa which made infarcts the commoner stroke type, but reflect those found in Blacks elsewhere in South Africa and America. Our results were achieved through the use of the CT scan as opposed to the earlier clinically-diagnosed West African studies. The larger number of haemorrhagic strokes had therapeutic implications. Trepidation in the use of anticoagulants, thrombolytics and fibrinolytics before proof of the pathological type is advised. Although clinical evaluation may be more cost-effective in the management of stroke, brain imaging techniques are recommended for accuracy in diagnosis and appropriate management.

Mylohyoid nerve damage due to excision of the submandibular salivary gland.

Two cases of damage to the mylohyoid nerve following the excision of submandibular salivary glands are presented. The distribution of analgesia over the chin, accompanied by normal sensation to the lip, indicated that the mylohyoid nerve was damaged.

Current trends in the incidence of cerebrovascular accidents in Accra.

The incidence of cerebrovascular accidents (CVA) in Accra during three periods--1960-1968, 1976-1983, and 1990-1993, was compared. There was dramatic increase in the incidence between 1990-1993. Uncontrolled hypertension due to non-compliance with drug therapy seems to be the main cause. The economic plight of the people may explain the non compliance. The case fatality was between 41.9% to 50.3% for the years 1990-1993. Cardiovascular diseases, notably hypertension and CVA, have become the major causes of morbidity and mortality in Accra.