Infection of Plasmodium falciparum and helminths among school children in communities in Southern and Northern Ghana.

BACKGROUND: Infections of Plasmodium species, Schistosoma species and soil-transmitted helminths (STH) inflict a significant burden on children mostly in deprived communities in Ghana. Despite the deployment of malaria vector control and the annual Mass Drug Administration by National Control Programmes, these infections still pose major public health concerns in Ghana. Some remote communities which are hard-to-reach are not covered by MDA campaigns which is a major challenge to meeting elimination targets. Adequate data is necessary for formulating policies and strengthening interventions to mitigate transmission. This study assessed the infection burden of Plasmodium, Schistosoma species and STH infections among school children in communities in Southern and Northern Ghana. METHOD: School children living in communities in Southern (Ada Foah, Pediatorkope, Tuanikope) and Northern (Kpalsogu) Ghana were enrolled in a cross-sectional study. A total of 493 (241 males and 252 females) school children aged (2-15 years) were enrolled in the study. Stool samples were collected to screen for Schistosoma mansoni and STH infections using the formol-ether concentration technique and urine samples were also collected to screen for S. haematobium using the routine urine examination method. Plasmodium parasitaemia was determined from thick and thin finger-prick blood samples. RESULTS: Overall, the prevalence of P. falciparum, S. mansoni, S. haematobium, Trichuris trichiura and hookworm infections were 17.2% (95%CI 12.8-19.7), 22.6% (95%CI 25.2-32.7), 1.6% (95%CI 0.89-5.2), 1.2% (95%CI 0.78-4.8) and 1.2% (95%CI 0.78-4.8) respectively. Plasmodium falciparum infection was generally widespread in all the study sites with Ada Foah recording the highest prevalence (35.3%) and Kpalsogu recording the lowest (5.8%). Schistosoma mansoni was present in only two Southern communities with Tuanikope recording the highest prevalence of 70.3% as against 51.5% recorded in Pediatorkope. A total of 4.5% (95% CI 2.82-10.8) of the children were co-infected with P. falciparum, Schistosoma species and STHs. This occurred only in the Southern communities; of which combination of P. falciparum and S. mansoni were predominant (1.4%). CONCLUSION: A relatively low burden of parasites co-infection among children only in the Southern communities was detected. However, there were a high prevalence of single infections of P. falciparum and S. mansoni in those communities. Control measures for the helminths needs to be restarted in the island communities with a high burden of S. mansoni infections and that of Plasmodium needs to be scaled up in Ada Foah where P. falciparum infections were high.

Dentistry, and why it is a great career.

The current climate of dentistry is one of sharply rising costs, increased litigation and more common placed stress, alongside the ever existing challenges that have persisted. This Opinion article looks into the reasons for embarking upon and staying within a dental career, despite the alleged drawbacks, and aims to promote a sense of positivity for the career that too often appears to be waning.

The safety, tolerability and pharmacokinetics of levamisole alone, levamisole plus ivermectin, and levamisole plus albendazole, and their efficacy against Onchocerca volvulus.

Two randomized, double-blind, placebo-controlled trials, in which levamisole (2.5 mg/kg) was given alone or co-administered with ivermectin (200 microg/kg) or albendazole (400 mg), were conducted. In Trial 1, safety and drug-drug interaction were explored in 42 healthy male volunteers. During Trial 2, the safety of the same treatment regimens and their efficacy against the adult worms and microfilariae of Onchocerca volvulus were investigated in 66 infected subjects of both sexes. Safety was determined from the results of detailed clinical and laboratory examinations before treatment, during hospitalization and on day 30. The pharmacokinetic parameters for levamisole alone and the combinations were determined in Trial 1 and then compared with historical data for ivermectin and albendazole, given as single agents, to determine if drug-drug interaction had occurred. The level of efficacy against the adult worms was determined by the examination of histology sections of nodules excised 6 months posttreatment and from the changes seen in the levels of microfilaridermia within a year of treatment. Microfilaricidal efficacy was estimated from the reductions in the levels of microfilaridermia between day 0 (1 day pre-treatment) and day 30. Although the regimens were generally well tolerated, there were unexpected adverse effects in both healthy volunteers and infected subjects. Clinically significant drug-drug interactions resulted in an increase in the bio-availability of ivermectin but a reduction in that of albendazole when these drugs were co-administered with levamisole. Levamisole given alone or with albendazole had little effect on O. volvulus. The combination of levamisole with ivermectin was neither macrofilaricidal nor more effective against the microfilariae and the adult worms than ivermectin alone. The pathogenesis of the adverse events and the drug-drug interactions are discussed.

Thirty-month follow-up of sub-optimal responders to multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana.

The pathogenesis of the sub-optimal response of Onchocerca volvulus to ivermectin was investigated in a 30-month follow-up of 28 individuals who, in a previous study, had been found to show a sub-optimal (N = 15) or adequate response (N = 13) to multiple treatments with the drug. Verbal informed consent was obtained before each subject was given a general clinical and ocular examination. Skin snips were taken from both iliac crests and both calves. Seventeen nodule carriers were hospitalized for nodulectomy. Adult worms were harvested, embryogrammes were constructed and all developmental stages were counted; degenerate, stretched microfilariae were noted separately. All the subjects were in good general health and all except one had received at least one additional treatment with ivermectin since the earlier study. A large proportion of the adult female worms in 10 out of the 11 sub-optimal responders who were nodule carriers were in full embryonic production but most of the stretched microfilariae they carried were degenerate. This picture is similar to that found in adult worms exposed to the first dose of ivermectin. In one subject who had no viable worms in his nodules, the existence of occult but actively reproductive worms was inferred from the high level of microfilaridermia observed less than 12 months after treatment. These observations confirm the existence of populations of adult female O. volvulus that respond poorly to repeated doses of ivermectin. The use of suramin in the treatment of the sub-optimal responders is discussed.

An investigation of persistent microfilaridermias despite multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana.

If ivermectin-based programmes for the control of human onchocerciasis are to be successful, the drug must remain effective for as long as necessary. In an open, case-control study, an attempt was made to determine if the persistent, significant, Onchocerca volvulus microfilaridermias seen in some individuals who had received at least nine treatments with ivermectin were the result of the development of drug resistance in the parasite. Twenty-one of these 'sub-optimal' responders (cases) were matched, by age, weight, number of treatments, locality and skin microfilarial counts, with seven amicrofilaridermic responders and 14 ivermectin-naive subjects. The number of treatments taken, any potential drug interactions and significant underlying disease were determined from detailed clinical and laboratory studies. Each subject was treated with ivermectin during the study, so that plasma concentrations of the drug could be determined for 72 h from the time of dosage. The microfilarial and adult-worm responses to this treatment were assessed from skin microfilarial counts (obtained before the treatment and at days 8, 90 and 365 post-treatment), day-90 embryogrammes, and the results of fly-feeding experiments. Parasite-sensitivity criteria for various time-points were derived from earlier data on skin microfilaridermias and the effects of ivermectin on the adult worms. The results indicate that the significant microfilaridermias that persist despite multiple treatments with ivermectin are mainly attributable to the non-response of the adult female worms and not to inadequate drug exposure or other factors. The possibility that some adult female worms have developed resistance to ivermectin cannot be excluded. These results justify the routine monitoring of treatment efficacy in any ivermectin-based programme of disease control.

The co-administration of ivermectin and albendazole--safety, pharmacokinetics and efficacy against Onchocerca volvulus.

A randomized, double-blind, placebo-controlled trial was conducted, to determine whether the co-administration of ivermectin with albendazole is safe and more effective against Onchocerca volvulus than ivermectin alone, and whether a significant pharmacokinetic interaction occurs. Forty-two male onchocerciasis patients received ivermectin (200 mug/kg) alone, albendazole (400 mg) alone or the combination. Safety was determined from the results of detailed clinical and laboratory examinations before treatment, during hospitalization and on day 30. Microfilaricidal efficacy was estimated from the reductions in skin counts between day 0 (pretreatment) and day 30. To determine efficacy against the adult worms, two independent observers examined histology slides prepared from nodules excised on day 180; changes in the skin counts of skin microfilariae between days 30 and 365 provided additional indicators of the level of adulticidal activity. Pharmacokinetic parameters for ivermectin and albendazole sulphoxide were defined over 72 h post-treatment. The co-administration of ivermectin with albendazole did not produce more severe adverse effects than ivermectin alone. Both nodule examiners found that the combination was not macrofilaricidal and that it was not clearly superior to ivermectin alone in the effects on reproductive activity; this was supported by the similar efficacy of the two regimens in the suppression of skin microfilariae. There was no significant pharmacokinetic interaction. Although the co-administration of ivermectin with albendazole appears safe, it offers no advantage over ivermectin alone in the control of onchocerciasis. The combination does not require an alteration in the dosage of either component.

The effects of high-dose ivermectin regimens on Onchocerca volvulus in onchocerciasis patients.

Ivermectin, at the standard dose of 150 micrograms/kg bodyweight, does not kill the adult worms of Onchocerca volvulus and does not disrupt embryogenesis or spermatogenesis. Repeated standard doses, if maintained, arrest microfilarial production but result in only a mild-to-modest macrofilaricidal effect. We investigated whether high doses would effectively kill the adult worms, and whether cessation of microfilarial production could be reproduced by an equivalent, single, high dose. One hundred men participated in a double-blind placebo-controlled trial and received increasing doses of ivermectin from 150 micrograms/kg to 1600 micrograms/kg bodyweight. Nodules were excised at day 180 and examined by histopathology. Total doses of ivermectin up to 1600 micrograms/kg were not significantly more effective than 150 micrograms/kg. Moreover, they did not reproduce the marked inhibitory effects of the repeat standard-dose regimens on embryogenesis, nor the modest effect on adult worm viability, at comparable total doses. These effects may be functions of multiplicities of dosages rather than of the total dose. Our findings also suggest that repeated high-dose regimens are unlikely to be more effective than a similar number of 150 micrograms/kg doses. This deficiency of ivermectin requires that the search for macrofilaricides remains a top priority.

Chemotherapy for onchocerciasis: results of in vitro experiments with promising new compounds.

An improved short-term in vitro culture system was used for the routine screening of hundreds of promising new compounds with the target organism, the filarial nematode Onchocerca volvulus. The most active leads were identified among the pyrimidinylguanidines, amidine derivatives, the imidazolinylhydrazones, thiosemicarbazone derivatives and thiadiazole derivatives. Single compounds of these leads demonstrated strong macrofilaricidal efficacy in minimum effective dose trials down to 0.1 microM and in experiments evaluating the minimum time of exposure after less than 6 h exposure. In the group of the pyrimidinylguanidines we found a significant correlation of structure and activity: change of a single side-group in the molecules had dramatic influence on compound activity. Most of the new compounds that were active on the macrofilariae did not show significant activity on microfilariae (mf) in in vitro trials. Only one compound with significant activity against female O. volvulus worms killed mf at very low concentrations. Some of the promising leads will be processed in further trials on a preclinical level with predictive cattle models.

The safety and efficacy of amocarzine in African onchocerciasis and the influence of ivermectin on the clinical and parasitological response to treatment.

The hundred men from a forest area of Ghana, without vector control or ivermectin distribution, were randomized to receive a single dose of ivermectin (150 micrograms/kg body weight) on day 1 followed by amocarzine (3 mg/kg twice daily after meals) on days 8, 9 and 10 (34 patients), the ivermectin alone (33 patients) or the amocarzine alone (33 patients). Detailed clinical and laboratory examinations were made before, during and after drug administration. On day 120, all palpable nodules were excised, fixed, sectioned, stained and examined by two blinded observers and the results compared with those for nodules from untreated controls. Mazzotti-type reactions, such as itching, rash, peripheral sensory phenomena and swellings, were more severe or frequent with amocarzine than ivermectin. Pretreatment with ivermectin markedly suppressed these reactions to amocarzine but did not affect other manifestations such as dizziness and gaze-evoked nystagmus. Ocular effects were minor in all groups. Ivermectin produced minor macrofilaricidal effects on the adult male worms, marked degeneration of intra-uterine embryos, and potent microfilaricidal effects and suppressed skin microfilariae. Amocarzine did not affect the male worms or the intra-uterine embryos, was a less potent microfilaricide and did not suppress skin microfilariae. The efficacy of ivermectin plus amocarzine was similar to that of ivermectin alone. The present results do not support the findings from the Americas and show that amocarzine has no role in the treatment of onchocerciasis in Africa.

The anterior central nervous system of male Onchocerca volvulus (Nematoda:Filarioidea) as a target for chemotherapy: results of an electron microscopy study.

An electron microscopy study was performed to evaluate the feasibility of the use of the anterior nerve ring of male Onchocerca volvulus for the assessment of early drug effects. Worms were exposed to new and known compounds at reasonable concentrations of 1 microM and less for 6, 12, 18, and 36 h in an established in vitro system. The anterior end of the filariae up to a length of 1 mm was examined and the morphological findings were compared with motility and reduction of a tetrazolium sat to formazan by live but not dead worms. The nerve fibers were more susceptible to the chemotherapeutic intervention then the other tissues in the anteriormost part of the worms. The alterations depended on the duration of exposure and the chemical nature of the compounds used. Morphological changes in the nervous tissue and the inhibition of motility and formazan production corresponded well for the arsenical mel w, used as an active standard, two pyrimidinyl-guanidines (PD 105482 and PD 105666), and an imidazolinylhydrazone (WR 251993).

The ultrastructure of the anterior end of male Onchocerca volvulus: papillae, amphids, nerve ring and first indication of an excretory system in the adult filarial worm.

A detailed morphological investigation of the anterior sensory organs, the nerve ring and a glomerulus-like structure in male Onchocerca volvulus was performed by means of electron microscopy. The 8 head papillae are arranged in the common 4 + 4 pattern of most filarial worms in circles around the mouth opening. The amphidial openings are found between the circles of inner and outer papillae on both sides of the mouth. Inside, several additional nerve axons are seen in the tissue of the anterior tip not related to one of the identified papillar structures. The inner and outer papillae exhibit a remarkably different fine structure, and are part of a complex system of at least 2 different receptor cell types at the anterior tip of the worm. The amphidial channel contains 8 modified cilia; accessory axons are associated with the cytoplasm of the sheath cell. The anterior nerve ring of male worms is located about 150 micrometers posterior from the outermost tip of the head region. It consists of several fibres coiled around the oesophagus. The comparison of the fine structure of the central nervous system did not show the expected morphological differences associated with the heterogeneous age distribution in the natural worm population. This was in contrast to previous findings with respect to tissues in different parts of the worm. The study also provides the first evidence that suggests the existence of an excretory organ in a filarial worm in the region of the anterior nerve ring. Paired glomerulus-like structures in the lateral chords and a canal formed by a projection of the basal zone of the cuticles were identified.