Low-dose lisinopril in normotensive men with idiopathic oligospermia and infertility: a 5-year randomized, controlled, crossover pilot study.

The outcomes of drug treatment for male infertility remain conjectural, with controversial study results. Our pilot study employed a randomized, placebo-controlled, crossover methodology with intention-to-treat analysis. Thirty-three men with idiopathic oligospermia were randomized to start either daily oral lisinopril 2.5 mg (n = 17) or daily oral placebo (n = 16). Lisinopril was found to cause a normalization of seminal parameters in 53.6% of the participants. Although the mean ejaculate volume was unchanged (P ≥ 0.093), the total sperm cell count and the percentage of motile sperm cells increased (P ≤ 0.03 and P < 0.001, respectively), whereas the percentage of sperm cells with abnormal morphology decreased (P ≤ 0.04). The pregnancy rate was 48.5%, and there was no serious adverse drug event. It is concluded, albeit cautiously, that prolonged treatment with 2.5 mg/day of oral lisinopril may be well tolerated in normotensive men with idiopathic oligospermia, may improve sperm quantity and quality, and may enhance fertility in approximately half of those treated.

Interference by malaria in the diagnosis of typhoid using Widal test alone.

A total of 270 febrile patients (130 males and 140 females) aged between 15 and 59 were screened using thick and thin blood film stains for malaria, bacteriologic culture and Widal test for enteric fevers. Sixty (22%) were positive for malaria while 38 (14%) were positive for enteric fevers out of which 16 (26.6%) concomitantly had malaria parasite. Cases without malaria parasite (MP) or enteric fever organism were 172 (63.7%) and classified as pyrexia of unknown origin (PUO). Forty-four were strictly malaria cases out of which 36 (82%) were due to Plasmodium falciparum, and all had antibody Widal titres > or = 160 to 0 antigen while 4 (9%) were due to Plasmodium malariae, 3 (6.8%) were due to P. ovale and 1 (2.3%) was due to P. vivax. Twenty (52.6%) of the 38 patients with enteric fever had typhoid, all had Widal titres > or = 160 to 0 antigen. In all, antibody reaction Widal titres to H antigen were < 20. There was no statistical significant difference [chi2 = 327.2, P > 0.05] between Widal titres of malaria and typhoid cases. Hence using Widal test alone, one cannot differentiate typhoid fever from malaria. In another 250 healthy adults, of equal sex distribution, used as controls 12 (4.8%) had malaria parasite and 4 (1.6%) had enteric fever organisms. While only 4 (1.6%) gave Widal titre of 80 to 0 antigen the rest had antibody titres of < 20 to O antigen. Malaria could interfere with serological diagnosis of typhoid and hence lead to over diagnosis of typhoid in Nigeria.

Community-based ivermectin therapy for onchocerciasis: comparison of three methods of dose assessment.

A new method of assessment based on mid-upper arm circumference (MUAC) is described for dosage adjustment for community-based ivermectin distribution. We studied 878 subjects eligible for ivermectin dosing in Awhum, Nigeria. In a previous preliminary study of 40 persons, MUAC (in cm) correlated with weight (kg) in the first 20 male (r = 0.97, r2 = 0.95, P < 0.0001) and the first 20 female subjects (r = 0.94, r2 = 0.88, P < 0.0001). We therefore studied the use of height, physical appearance, and MUAC for calculating the dose of ivermectin. The MUAC-based schedule underdosed only 4.1% of the population. The methods based on height underdosed 3.3% and 21.1%, and assignment based on physical appearance underdosed 10.2% of the population studied. This MUAC-based method (13-15 cm, 0.5 tablet; 16-20 cm, 1.0 tablet; 21-27 cm, 1.5 tablets; > or = 28 cm, 2.0 tablets) is more convenient and corresponds closely to dosing by weight. An adaptation of this method with reference to other prevalent tropical diseases and their respective drugs is therefore advocated.

Compliance to correct dose of chloroquine in uncomplicated malaria correlates with improvement in the condition of rural Nigerian children.

Non-compliance to correct dosing is thought to be one of the main causes of treatment failure of chloroquine in the home management of childhood malaria. There are few studies of compliance to drugs used for tropical diseases. In order to study compliance in the rural setting, chloroquine syrup was packaged with a novel pictorial insert for compliance to correct dosing. Compliance was assessed in a field trial in September 1996-December 1997, involving 632 children with uncomplicated malaria in Udi local government area in Nigeria. Written informed consent was obtained from mothers/guardians before children were enrolled in the study. There were 3 arms to the trial: control villages (group I) received chloroquine syrup without further intervention, group II received a pictorial insert with chloroquine syrup, and group III received chloroquine syrup, the pictorial insert and verbal instructions. Each group was made up of 3 health centres. Compliance was assessed by volumetric measurement of the chloroquine syrup left in 30-mL bottles and by questionnaires administered to mothers/helpers of the children. Control villages recorded full compliance for 36.5 +/- 4.4% of the children, group II for 51.9 +/- 7.9% and group III for 73.3 +/- 4.2%. There was a significant correlation (P < 0.0001) between full compliance, improvement and time for improvement of the condition. This study is deemed important because it focuses on children, who bear the greatest burden of malaria. It is unique for introducing a pictorial insert that illiterate villagers, who may not understand the use of age or weight in drug dispensing, may utilize as a substitute.

How do rural households perceive and prioritise malaria and mosquito nets? A study in five communities of Nigeria.

The aim of this study was to determine households' levels of prioritization and perception of malaria, ordinary mosquito nets and insecticide-treated nets (ITNs). A cross-sectional survey was conducted in five malaria holo-endemic communities in Enugu State, South-eastern Nigeria. The household heads or the representatives from randomly selected households were interviewed, using a pre-tested interviewer-administered questionnaire. The majority of the respondents had a good knowledge about malaria and the use of ordinary mosquito nets to prevent malaria. However, few knew about the existence of ITNs. Most respondents also stated that malaria was a priority problem and perceived some risk of contracting it. Despite the high level of knowledge about the use of mosquito nets, only 14.0%, 15.7%, 9.6% and 8.0% of the respondents from four of the communities had ever purchased any type of mosquito nets, except in Orba where the proportion was 50.3%. However, more than 80% in all the communities expressed a desire to buy insecticide-treated mosquito nets for the prevention of mosquito bites. There was considerable knowledge about malaria and the use of mosquito nets to prevent it. There were also high levels of prioritization of the disease, mosquito nets and ITNs which signalled the possibility of establishing sustainable community-based ITN programmes, especially as households wanted to buy the ITNs.

Community financing of local ivermectin distribution in Nigeria: potential payment and cost-recovery outlook.

The preferred payment mechanism in a community financing scheme for local ivermectin distribution was elicited from randomly selected household heads from three communities in Nigeria using interviewer-administered structured questionnaires. The majority of the respondents in the three communities were prepared to pay for local ivermectin distribution. Additionally, the average amounts the respondents were prepared to pay per person treated ($0.28, $0.30 and $0.38 in Nike, Achi and Toro, respectively) were all more than the $0.20 ceiling recommended by the partners of the African Programme on Onchocerciasis Control (APOC). Thus, the cost-recovery outlook is bright in these communities. However, the preferred payment modality varied. Fee-for-service was the predominant payment modality in the Achi and Nike communities, while the Toro community preferred pre-payment. This study demonstrates that many communities have different payment preferences for endemic disease control efforts. This knowledge will help in developing acceptable and sustainable schemes. The imposition of unacceptable payment mechanisms will lead to an unwillingness to pay.

A health club for a community school in south-eastern Nigeria: influence on adult perception of onchocerciasis and compliance with community-based ivermectin therapy.

The impact of a school health club on adult perception of onchocerciasis and compliance with ivermectin was evaluated in an onchocerciasis-endemic community in southeastern Nigeria. Venous blood was collected from each of 26, 32 and 124 randomly selected subjects during ivermectin distribution programmes in 1995 1996 and 1997 respectively. Ivermectin concentrations were measured in the samples. Data was also collected from 334 and 319 randomly selected household heads or their representatives (aged 24 to 65 years) before and after health talks by schoolchildren, using interviewer-administered questionnaires. There was an increasing number of subjects who participated in control programmes (116 in 1995, 437 in 1996 and 2055 in 1997). Compliance with ivermectin treatment was low (53.9%) in 1995 but increased dramatically (90.1%) in 1997. A significant proportion (chi2 = 108.7, df = 1, P < 0.0001) of respondents knew about onchocerciasis after health education, predominantly from health workers (64.5%) before the tests and children (92.3%) after. Knowledge and beliefs about causative agents (chi2 = 266.4, df = 5, P < 0.0001), diagnostic method (chi2 = 207.4, df = 3, P < 0.0001), prevention (chi2 = 67.0, df = 4, P < 0.0001) of onchocerciasis and the effectiveness of ivermectin (chi2 = 40.4, df = 1, P < 0.0001) also differed significantly between the periods before and after tests. The school health club increased adult knowledge about onchocerciasis and its treatment. Schoolchildren could therefore supplement the information, education and communication (IEC) aspect of health care delivery in a community through such health clubs.

Ivermectin: concentration-dependent effects on adenosine triphosphatases in adult worms of Onchocerca volvulus.

The effect of increasing concentrations of ivermectin on adenosine triphosphatase (ATPase) activity was investigated in adult worms of Onchocerca volvulus. Mean Mg- and Na,K-ATPase activities decreased significantly (F ratio = 29.82, P < 0.01 and F ratio = 28.54, P < 0.01, respectively) with increasing concentrations of ivermectin (0-100 ng/ml) in the female worms. When male and female worms were mixed with equal amounts of proteins from each, only the Na,K-ATPase activity was significantly decreased (F ratio = 56.61, P < 0.01) over a similar range of ivermectin concentrations. Since ivermectin exhibits concentration-dependent effects on both ATPases in female adult worms, this might provide an insight into other effects of the drug. However, the adjustment of the dose of ivermectin to obtain a nodular concentration of at least 40 ng/ml is therefore recommended in the complete chemotherapy of onchocerciasis.

Health education to school children in Okpatu, Nigeria: impact on onchocerciasis-related knowledge.

We assessed the influence of health education on the knowledge about onchocerciasis in school children in Okpatu, Nigeria. The children, aged between 11 and 17 y, received health education in both English and Igbo (local language) for three months on the transmission, clinical manifestations, treatment and prevention of onchocerciasis. Illustrated pictorial materials were used to support and enhance their understanding of the subject matter. Their level of knowledge was evaluated nine months later using a pre-tested personal interview administered questionnaire. A significantly higher proportion of these children knew about onchocerciasis (chi2=260.4, df=1, P<0.0001), and its causative agent (chi2=175.0, df=4, P<0. 0001), clinical manifestations (chi2=254.0, df=5, P<0.0001), diagnosis (chi2=123.9, df=2, P<0.0001), treatment (chi2=197.8, df=3, P<0.0001) and prevention (chi2=220.8, df=3, P<0.0001) in the post- than in the pre-educational intervention. It is therefore concluded that school-based health education showed an increase in knowledge about onchocerciasis and school children could provide a useful 'multiplier' resource for health education in the community.

Willingness to pay for the maintenance of equity in a local ivermectin distribution scheme in Toro, Northern Nigeria.

The willingness to pay (WTP) for the maintenance of equity in a local ivermectin distribution scheme in the context of a community financing framework was determined in Toro, Northern Nigeria, using 214 randomly selected heads of households, or their representatives. Though WTP of the respondents for their own households was elicited, the focus of this paper is on WTP to maintain equity in a community financing scheme. Contingent valuation was used for the exercise, and WTP was elicited using an open-ended question. 97.2% of the respondents were in favour of allowing those that lack the ability to pay, to benefit from the scheme and the maximum WTP amounts they were willing to contribute annually so that those who lack the ability to pay could benefit from the scheme ranged from 5 Naira ($0. 06) to 100 Naira ($1.25). The mean WTP to maintain equity was 29.00 Naira ($0.36) while the median was 20.00 Naira ($0.25). This study shows that a community financing scheme for local ivermectin distribution will not be inequitable, since enough funds will be realised from well-to-do community members to cover the costs for those who are unable to pay.

PIP: The willingness to pay (WTP) for the maintenance of equity in local ivermectin distribution scheme in the context of a community financing framework was determined in Toro, northern Nigeria, using 214 randomly selected heads of households or their representatives. The focus of this paper is to maintain WTP equity in a community financing scheme. Contingent evaluation was used for the exercise, and WTP was elicited using an open-ended question. The result of the study indicates that 92% of the respondents were willing to pay to benefit from the scheme by contributing a certain amount annually. The mean stated WTP to maintain equity was 29.00 naira, while the median was 20.00 naira. Therefore, the collective WTP amounts should be adequate to cover the costs of distributing ivermectin to the indigent community members annually. This study shows that a community financing scheme may not be inequitable if areas for raising funds for the indigent community members are discovered.

Influence of health education on community participation in rapid assessment of onchocerciasis prior to distribution of ivermectin.

OBJECTIVE: To investigate the impact of health education on community participation in the rapid assessment of onchocerciasis prior to distribution of ivermectin in Nigeria. DESIGN: There was health education with use of pictorial monographs to an adult population and school children in Umulumgbe and Okpatu communities, respectively. The school children in turn transferred the knowledge acquired to their parents through a health club, and a third community (Awhum) had no health education. Randomly selected subjects in each community were then assessed for their ability to recognise clinical manifestations of disease. SETTING: The study took place in three onchocerciasis-endemic, autonomous communities in Udi local government area of Enugu state in eastern Nigeria. SUBJECTS: Fifty, thirty seven, and thirty three male subjects, aged 20 years and above in Umulumgbe, Okpatu and Awhum respectively were involved in the study. RESULTS: 89.3%, 100% and 25.6% of the total number of onchocercal nodules were rightly indicated by the subjects in Umulumgbe, Okpatu and Awhum respectively. 100% of skin depigmentation was also reported in Umulumgbe and Okpatu each, and 50% in Awhum. Although some of the clinical manifestations (onchocercal nodules and skin depigmentation) were wrongly indicated, others (hanging groin and enlarged scrotum) were not reported by the subjects at all. CONCLUSION: This study clearly shows that health education is necessary for control programmes that are meant to be sustainable, especially the WHO-supported community-directed treatment with ivermectin (CDTI).

PIP: This article examines the impact of health education on community participation in the rapid assessment of onchocerciasis before distributing ivermectin in Nigeria. The study was conducted in three onchocerciasis-endemic areas of Nigeria--Awhum, Umulumgbe, and Okpatu--involving 33, 50, and 37 male subjects, respectively, in each community. A health education activity on onchocerciasis was conducted among the adult population and school children of Umulumgbe and Okpatu communities, after which, a rapid assessment of onchocerciasis was carried out. On the other hand, a rapid assessment was also conducted in Awhum in March 1995 before ivermectin distribution without prior health education. The study found that onchocercal nodules were more frequent in the lower part of the subject's body, especially around the pelvic region. Onchocercal nodules were indicated by 89.3% of the subjects in Umulumgbe, by 100% of the subjects in Okpatu, and by 25.6% of the subjects in Awhum. Skin pigmentation was also reported by 100% of the subjects in Umulumgbe and Okpatu and by 50% of the subjects in Awhum. The investigation discovered that some onchocercal nodules were incorrectly identified by the three communities, resulting in failure of reporting other clinical manifestations of the disease. Despite these limitations, researchers still feel that health education greatly influenced their knowledge on the parasitic disease.

Willingness to pay for community-based ivermectin distribution: a study of three onchocerciasis-endemic communities in Nigeria.

OBJECTIVE: To determine the willingness to pay (WTP) for local ivermectin distribution in a community financing framework. METHOD: Contingent valuation in three communities in Nigeria, using randomly selected household heads. WTP was elicited using a bidding game, and for collecting information on the households' socio-economic status, level of knowledge, priority ranking and perception of risk of contracting the disease, structured questionnaires were used. Ordinary least squares (OLS) multiple regression analysis was used to analyse factors associated with WTP. RESULTS: Between 92.1% and 93.3 % of respondents were willing to pay amounts ranging from 5 Naira (US$ 0.06) to 100 Naira (US$ 1.25) (median: 20 Naira, US$ 0.25) in the three communities, more than three times the modelled unit direct cost of distributing ivermectin by the communities themselves. Occupation of the respondent, marital status, average monthly expenditure on health care, manifestations of onchocerciasis, the type of savings scheme embarked on by the respondent, age-group, level of education and type of property were statistically significant (P < 0.05) variables affecting WTP. CONCLUSION: This study shows that there is WTP for local ivermectin distribution in the three study communities, and that it should be assessed before instituting community-directed treatment with ivermectin.

Clinical pharmacokinetics of suramin in patients with onchocerciasis.

OBJECTIVE: Ten male patients with onchocerciasis received six weekly infusions of suramin according to the WHO-recommended regimen. RESULTS: In no case did the plasma concentration of suramin exceed 300 mg x l(-1), and serious toxicity was not observed. The apparent volume of distribution (median 20.6 l) was comparable to that reported for patients with prostatic carcinoma. Elimination from patients with onchocerciasis was relatively slow (median plasma clearance 6.2 ml x h(-1), median terminal elimination half-life 91.8 days). CONCLUSION: Microfilariae were eliminated in eight out of ten patients. Spontaneous nodule regression was noted in four patients.

Fleroxacin vs Ciprofloxacin in the Management of Typhoid Fever: A Randomised, Open, Comparative Study in Nigerian Patients.

OBJECTIVE: The antibacterial efficacy of fleroxacin was compared with that of ciprofloxacin in 72 adult Nigerian patients with typhoid fever. PATIENTS AND METHODS: On inclusion into the study, patients were randomised to treatment with either fleroxacin 400mg once daily for 7 days or ciprofloxacin 500mg twice daily for 14 days. Clinical evaluations were performed on days 0, 1, 2, 3, 5 and 7 or 14, and 2 weeks after treatment. Bacteriology was performed on days 0, 3, 7 or 14, and 21 or 28. Laboratory tolerability parameters were monitored for all patients as well as incidence of adverse events. RESULTS: Bacteriological response on day 3 was 93.5 and 64.0% for fleroxacin and ciprofloxacin, respectively. At term and follow-up there was bacteriological cure in 97.0% of patients with fleroxacin and 100% with ciprofloxacin. The clinical cure was 100% for both groups at term. The incidence of adverse events was 5.4% with fleroxacin and 2.8% with ciprofloxacin. CONCLUSION: The results demonstrated that while the clinical response rate with both drugs was comparable, fleroxacin exhibited a faster bacteriological clearance rate. We therefore concluded that 7 days' therapy with fleroxacin 400mg once daily was as effective as 14 days' therapy with ciprofloxacin 500mg given twice daily in the management of typhoid fever in Nigerian patients. It was also observed that the quinolones possessed greater potential and benefits as first-line therapy for the management of typhoid fever in this environment. The tolerability profile was good for both treatment regimens.

An improved dosing schedule for ivermectin as a microfilaricidal agent against onchocerciasis.

The introduction of ivermectin therapy has proved to be the most important advance in the management and control of onchocerciaisis. By using the standard dosing schedule (150 micrograms/kg) in a mass chemotherapy campaign in Awhum, Nigeria, 128 (14.6%) of 875 eligible subjects used in this study were underdosed while 696 (79.6%) and 51 (5.8%) were overdosed and correctly dosed, respectively. Since underdosing is more serious than overdosing, an improved dosing schedule (300 micrograms/kg) is hereby suggested, bearing in mind that ivermectin is safe at doses well in excess of the standard dose. 824 (94.2%) And 51 (5.8%) of these eligible subjects would be overdosed and correctly dosed respectively, if this improved dosing schedule (< 15 kg, 0 mg (0 tablet); 15-20 kg, 6 mg (1 tablet); 21-40 kg, 12 mg (2 tablets); 41-60 kg, 18 mg (3 tablets); > 60 kg, 24 mg (4 tablets)) were to be employed. This dosing schedule is worth adopting and an investigation of the effects of these high single doses of ivermectin on adult Onchocerca volvolus worms is advocated. Furthermore 'non-responders' may be investigated for doses administered.

Eye disease in an onchocerciasis-endemic area of the forest-savanna mosaic region of Nigeria.

In a forest-saving mosaic zone of south-eastern Nigeria endemic for onchocerciasis, we identified eye disorders in 65.5% of a randomly selected population sample. Onchocerciasis-related eye disease was present in 13.7% of the study sample and constituted 21% of the total number of eye disorders. A total of 78 (33.2%) of 235 subjects with visual impairment had onchocerciasis-related eye lesions, and of 35 who were blind in both eyes, onchocerciasis-induced eye disease was the cause in 28 (80%). The prevalence of bilateral blindness from all causes in the study area was 4.1%, while that from onchocerciasis-related causes was 3.3%. The commonest onchocerciasis-induced lesions that were responsible for visual impairment and blindness were choroidoretinitis and optic nerve disease. Sclerosing keratitis, an important causative lesion in onchocerciasis-endemic savanna regions, was encountered only one. Eye disease is therefore an important feature of onchocerciasis in the forest-savanna mosaic areas of Nigeria and should be borne in mind when planning and executing control programmes.