Antibody response to 17D yellow fever vaccine in Ghanaian infants.

OBJECTIVES: To assess the seroresponses to yellow fever vaccination at 6 and 9 months of age; assess any possible adverse effects of immunization with the 17D yellow fever vaccine in infants, particularly at 6 months of age. METHODS: Four hundred and twenty infants who had completed BCG, OPV and DPT immunizations were randomized to receive yellow fever immunization at either 6 or 9 months. A single dose of 0.5 ml of the reconstituted vaccine was administered to each infant by subcutaneous injection. To determine the yellow fever antibody levels of the infants, each donated 1 ml whole blood prior to immunization and 3 months post-immunization. Each serum sample was titred on Vero cells against the vaccine virus. FINDINGS: The most common adverse reactions reported were fever, cough, diarrhoea and mild reactions at the inoculation site. The incidences of adverse reactions were not statistically different in both groups. None of the pre-immunization sera in both age groups had detectable yellow fever antibodies. Infants immunized at 6 months recorded seroconversion of 98.6% and those immunized at 9 months recorded 98% seroconversion. The GMT of their antibodies were 158.5 and 129.8, respectively. CONCLUSIONS: The results indicate that seroresponses to yellow fever immunization at 6 and 9 months as determined by seroconversion and GMTs of antibodies are similar. The findings of good seroresponses at 6 months without significant adverse effects would suggest that the 17D yellow fever vaccine could be recommended for use in children at 6 months in outbreak situations or in high risk endemic areas.

Consequences of hydrocele and the benefits of hydrocelectomy: a qualitative study in lymphatic filariasis endemic communities on the coast of Ghana.

A study using focus group discussions and in-depth interviews was conducted to determine the consequences of hydrocele and the benefits of hydrocelectomy on physical activity and social life in three lymphatic filariasis endemic villages where males had recently been offered surgical operations to repair their hydroceles. Respondents were of the view that hydrocele, especially large ones, severely reduced the patients' work capacity and impaired sexual function, and that overall it had a considerable negative effect on the quality of living for the patients, their families and the community. The main reasons for refusing hydrocelectomy in the past were the high cost of surgery, and to some extent fear of death, impotence and/or sterility that might result from the operation. The recently offered hydrocele operations, which included 40 males, were financially supported and preceded by appropriate counselling, and from the patients' point of view were highly successful. Patients spent between 4 and 12 days in the hospital and there were no post-operative complications. Patients observed that, between 3 and 6 months after surgery, there were remarkable improvements in their work capacity and sexual function, and restoration of self-esteem, thus enabling them to participate more actively in community activities. The need for hydrocelectomy to be incorporated as an important morbidity control measure in lymphatic filariasis control programmes is discussed.

Single-dose treatment of Wuchereria bancrofti infections with ivermectin and albendazole alone or in combination: evaluation of the potential for control at 12 months after treatment.

The effect of single-dose ivermectin (150-200 micrograms/kg) and albendazole (400 mg) treatment alone and in combination on Wuchereria bancrofti microfilaraemia, antigenaemia and clinical manifestations was compared 12 months after treatment in a double-blind placebo-controlled field trial carried out in Ghana in 1996-98, to evaluate the potential of these treatments for control. Both ivermectin and combination treatments resulted in pronounced reductions in microfilaraemia among individuals who were microfilaria positive before treatment. Among individuals who were positive for circulating filarial antigen before treatment, antigen levels increased considerably over the 1-year period after treatment in the placebo group, whereas they decreased in the ivermectin and combination groups. However, the post-treatment difference reached statistical significance in neither microfilaraemia nor antigenaemia between the ivermectin and the combination groups. Albendazole treatment alone showed only a minor effect on microfilaraemia and antigenaemia. No effect of the treatments on the incidence of new cases of microfilaraemia or antigenaemia, or on clinical manifestations, was observed. Both ivermectin and combination treatment thus appeared effective for control of W. bancrofti infections, but the difference in efficacy between the 2 treatments after 12 months appeared to be minimal.

Health centre versus home presumptive diagnosis of malaria in southern Ghana: implications for home-based care policy.

A study was conducted in 1997 to compare the accuracy of presumptive diagnosis of malaria in children aged 1-9 years performed by caretakers of the children to that of health centre staff in 2 ecological zones in southern Ghana. Similar symptoms were reported in the children at home and at the health centre. In the home setting, symptoms were reported the same day that they occurred, 77.6% of the children with a report of fever were febrile (axillary temperature > or = 37.5 degrees C) and 64.7% of the reports of malaria were parasitologically confirmed. In the health centre, the median duration of symptoms before a child was seen was 3 days (range 1-14 days), 58.5% of the children with a report of fever were febrile and 62.6% of the clinically diagnosed cases were parasitologically confirmed. In the 2 settings almost all the infections were due to Plasmodium falciparum. Parasite density was 3 times higher in the health centre cases compared to the home-diagnosed cases. Early and appropriate treatment of malaria detected in children by caretakers may prevent complications that arise as a result of persistence of symptoms and attainment of high parasitaemic levels.

A randomized double-blind placebo-controlled field trial of ivermectin and albendazole alone and in combination for the treatment of lymphatic filariasis in Ghana.

The efficacy and safety of single-dose ivermectin (150-200 micrograms/kg) and albendazole (400 mg) treatment administered separately or in combination for Wuchereria bancrofti infections were assessed in 1996-98 in a randomized double-blind placebo-controlled field trial in Ghana: 1425 individuals from 4 lymphatic filariasis-endemic villages, 340 of whom were microfilaria (mf)-positive before treatment, were randomized into 4 groups to receive albendazole alone, ivermectin alone, combination of albendazole and ivermectin, or placebo, respectively. Individuals were followed for 5 days after treatment to record any adverse reactions, and the effect of treatment on microfilaraemia was monitored in night-blood samples after 3, 6 and 12 months. Treatment efficacy was analysed for 236 mf-positive individuals who had > or = 100 mf/mL of blood and who were also present for examination at 12 months after treatment. Compared to the placebo group, the ivermectin and combination groups both showed statistically significant reductions in geometric mean mf intensities at the follow-up examinations (to 6.7% and 0.9%, 9.9% and 6.9%, and 21.7% and 11.4% of pre-treatment levels, respectively, at 3, 6 and 12 months after treatment). Compared to the ivermectin group, however, the reduction in the combination group was significantly greater only at 3 months after treatment, but not after 6 or 12 months. The albendazole group showed a slow but non-significant reduction over the same period. Adverse reactions were few and mostly mild (no severe reactions were recorded), and no significant differences were observed between the treatment groups. Both ivermectin and combination treatment thus appeared effective and safe for treatment of lymphatic filariasis, but the difference in efficacy was minor and the study did not provide clear evidence for the combination drug therapy, as compared to ivermectin therapy alone, to be superior for control of lymphatic filariasis.

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

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

Lymphatic filariasis related perceptions and practices on the coast of Ghana: implications for prevention and control.

A qualitative study to investigate lymphatic filariasis related perceptions and practices that may be relevant for the design of appropriate health education and control programmes was conducted in four endemic villages in coastal Ghana. The villagers were aware of the common manifestations of filariasis, such as adenolymphangitis (ADL), lymphoedema, elephantiasis and hydrocele, which were specifically described with local terminology. ADL attacks were identified as the most dreaded health problem in the communities, and elephantiasis and hydrocele also ranked high in importance among reported diseases. Generally the respondents did not accept the mosquito theory of transmission, but they believed in other physical, and in spiritual and hereditary causes. Hydrocele was considered to have no link to the other disease manifestations. The manifestations were most often treated with herbal preparations which were used orally, smeared on affected parts or given as enema. In some cases the affected parts were scarified before herbal preparations were applied. The manifestations affected the work output of its victims and subjected them to hardships such as teasing, unsuitability for marriage, sexual dysfunction and divorce. Although the etiology was seen as different, the local perception of the developmental process of elephantiasis closely paralleled that of the biomedical understanding. It is suggested that this coincidence is used as an entry point for health education, to advance a broader biomedical knowledge on etiology, transmission and treatment options, and thereby to ensure co-operation of the target populations in the control of this complex disease.

Comparative evaluation of three new tools for diagnosis of bancroftian filariasis based on detection of specific circulating antigens.

Three new and commercially available tools for diagnosis of Wuchereria bancrofti infections based on detection of specific circulating antigens were evaluated and compared in the same group of individuals from a highly endemic village in southern Ghana. The tests were: (1) the ICT card test for serum specimens; (2) the TropBio ELISA test for serum specimens; and (3) the TropBio ELISA test for filter-paper specimens. A high degree of positive/negative response similarity was observed for the 3 tests, and the sensitivity for detecting microfilaraemic cases was 100% for all tests. The antigen levels measured in the TropBio serum test and the TropBio filter-paper test were statistically significantly correlated. Among antigen-positive endemic individuals the antigen levels in these 2 tests furthermore showed a positive association with the microfilarial intensity, but a statistical significant correlation was seen only for the filter-paper version of the test. The results are promising for the use of the 3 tests as diagnostic tools in bancroftian filariasis.

Bancroftian filariasis in an irrigation project community in southern Ghana.

An epidemiological study to document the endemicity and transmission characteristics of bancroftian filariasis was conducted in an irrigation project community in southern Ghana. In a 50% random sample of the population, the prevalence of microfilaraemia was 26.4% and the geometric mean microfilarial intensity among positives was 819 microfilariae/ml of blood. Hydrocoele was found in 13.8% of the males aged > or =18 years, and 1.4% of the residents examined, all females, had tymphoedema/elephantiasis. Detailed monitoring of the microfilarial intensity in 8 individuals over a 24-h period confirmed its nocturnal periodicity with a peak at approximately 0100 hours. The most important vector was Anopheles gambiae s.l., followed by An. funestus. The abundance of these mosquitoes and their relative importance as vectors varied considerably between the wet and the dry season. Opening of the irrigation canals late in the dry season resulted in a remarkable increase in the population of An. gambiae (8.3% of which carried infective filarial larvae) to levels comparable to those seen during the wet season, suggesting that the irrigation project is responsible for increased transmission of lymphatic filariasis in the community.

A study on the provocative day test effect of ivermectin and albendazole on nocturnal periodic Wuchereria bancrofti microfilaraemia.

We conducted a randomized double-blind placebo-controlled study, in the Ahanta West District of Ghana, on the provocative day test effect of ivermectin and albendazole alone and in combination on nocturnal periodic Wuchereria bancrofti microfilaraemia. Sixty-three individuals with high night-time microfilaria (mf) intensities were identified in 1997 or 1998 and randomized into 4 groups. Blood samples for mf were then collected from the same individuals in the daytime (between 09:00 and 15:00) immediately before and 30-50 min after treatment. Groups 1-4 were treated with ivermectin alone (150-200 micrograms/kg), albendazole alone (400 mg), the combination of ivermectin and albendazole, and placebo, respectively. Intensities of mf in daytime samples were considerably lower than in night-time samples. Neither ivermectin or albendazole alone nor their combination provoked significant liberation of W. bancrofti mf into the peripheral circulation after the daytime treatment.

Comparison of AIK-C measles vaccine in infants at 6 months with Schwarz vaccine at 9 months: a randomized controlled trial in Ghana.

In a randomized controlled trial in a measles endemic area, standard-dose (4.0 log10pfu) AIK-C measles vaccine administered at 6 months of age was compared to standard-dose Schwarz vaccine (3.7log10pfu) given at 9 months. Seroconversion rates at 3 and 6 months after immunization in the two groups were comparable and similar. The geometric mean titres achieved were, however, significantly higher in the Schwarz group (P < 0.05). No immediate serious side-effects were observed with either vaccine. We conclude that standard-dose AIK-C measles vaccine can be recommended for measles immunization in children below 9 months of age, especially in highly endemic and high-risk areas in developing countries.

PIP: The seroresponse of standard-dose heat-stable AIK-C measles vaccine administered to infants at 6 months of age was compared to that of standard-dose Schwarz vaccine administered at 9 months of age in a measles-endemic area in West Africa. The study was conducted in Asamankese, the capital town of Ghana's East Akim District. Infants 24-27 weeks of age who had been attending the Asamankese maternal-child health clinic regularly and had received all the required immunizations were enrolled and randomly assigned to receive the AIK-C (n = 184) or the Schwarz (n = 193) vaccine. No severe adverse reactions were reported during the 10-day follow-up period in either vaccine group. In the AIK-C group, 96.9% of infants who were seronegative at preimmunization and 79.4% of those with preexisting antibodies had seroconverted by 3 months after immunization; at 6 months after immunization, these rates were 97.3% and 100%, respectively. In the Schwarz group, 98.2% of infants seronegative at immunization and 100% of those with preexisting antibodies seroconverted by 3 months after immunization; at 6 months, these rates were 99.1% and 80%, respectively. Although the geometric mean titres achieved were significantly higher in the Schwarz vaccine group, these titres were above the protective level of 200 mIU in the AIK-C group. Administration of measles vaccine at a younger age may be more easily incorporated into current Expanded Program on Immunization schedules.

Biliary excretion in persons with low blood glutathione levels.

A study to investigate the association between blood glutathione (GSH) levels and biliary excretory status was conducted in apparently healthy Ghanaian subjects without frank biliary disease and anaemia. The results showed that, in adults (mean age: 38.5 years) and children (mean age: 13.0 years), plasma conjugated bilirubin is inversely correlated with blood GS (respective site r = -0.524, p < 0.011 and -0.395, p < 0.005). Persons with elevated plasma conjugated bilirubin compared to controls (mean: 6.0 versus 2.5 umol/L, p < 0.001) also exhibited low blood GSH values (3.5 versus 4.2 umol/gHb, p < 0.029). Malaria parasites with counts up to 2,453 parasites/ul blood had no effect on the obtained data. The results suggest that low blood GSH levels may be relevant to delays in biliary excretion of conjugated toxins from the liver, as exemplified by the rise in conjugated bilirubin levels in the plasma, and predispose liver cells to increased oxidant state and damage.

Increased eosinophil activity in acute Plasmodium falciparum infection--association with cerebral malaria.

To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM (geometric mean (95% confidence interval) 8.5 ng/ml (6.8-10.7 ng/ml)) than in SA (4.7 ng/ml (3.0-7.5 ng/ml)) and UM patients (4.3 ng/ml (3.6-5.3 ng/ml), P < 0.001). A similar pattern was found for EPX. It thus appears that the low eosinophil counts may be due to tissue sequestration and destruction rather than decreased production. The plasma levels of the granule proteins correlated with levels of tumour necrosis factor and soluble IL-2 receptor, implicating inflammatory responses and T cell activation as causes of the eosinophil activation. By contrast, the eosinophil induction did not appear to be part of a Th2-like response. Eosinophil granule proteins may be important in both control of malaria infection and the pathogenesis of severe malaria.

Malaria-related beliefs and behaviour in southern Ghana: implications for treatment, prevention and control.

A research infrastructure was established in two ecological zones in southern Ghana to study the variables of malaria transmission and provide information to support the country's Malaria Action Plan (MAP) launched in 1992. Residents' beliefs and practices about causes, recognition, treatment and prevention of malaria were explored in two ecological zones in southern Ghana using epidemiological and social research methods. In both communities females constituted more than 80% of caretakers of children 1-9 years and the illiteracy rate was high. Fever and malaria, which are locally called Asra or Atridi, were found to represent the same thing and are used interchangeably. Caretakers were well informed about the major symptoms of malaria, which correspond to the current clinical case definition of malaria. Knowledge about malaria transmission is, however, shrouded in many misconceptions. Though the human dwellings in the study communities conferred no real protection against mosquitoes, bednet usage was low while residents combatted the nuisance of mosquitoes with insecticide sprays, burning of coils and herbs, which they largely considered as temporary measures. Home treatment of malaria combining herbs and over-the-counter drugs and inadequate doses of chloroquine was widespread. There is a need for a strong educational component to be incorporated into the MAP to correct misconceptions about malaria transmission, appropriate treatment and protection of households. Malaria control policies should recognize the role of home treatment and drug shops in the management of malaria and incorporate them into existing control strategies.