Search

Here, the authors develop a mouse model of Loa loa that reflects human infections, including eosinophilia, and determine effects of ivermectin treatment.

Background : Onchocerciasis elimination through mass drug administration (MDA) is hampered by coendemicity of Loa loa, as people with high L. loa microfilariae (mf) density can develop serious adverse events (SAEs) after ivermectin treatment. We assessed the geographical overlap of onchocerciasis and loiasis prevalence and estimated the number of coinfected individuals at risk of post-ivermectin SAEs in West and Central Africa from 1995 to 2025. Methods : Focusing on regions with suspected loiasis transmission in 14 countries, we overlaid precontrol maps of loiasis and onchocerciasis prevalence to calculate precontrol prevalence of coinfection by 5 km2 × 5 km2 pixel, distinguishing different categories of L. loa mf intensity. Using statistical and mathematical models, we predicted prevalence of both infections and coinfection for 2015 and 2025, accounting for the impact of MDA with ivermectin. Results : The number of people infected with onchocerciasis was predicted to decline from almost 19 million in 1995 to 4 million in 2025. Of these, 137 000 people were estimated to also have L. loa hypermicrofilaremia (>-20 000 L. loa mf/mL) in 1995, declining to 31 000 in 2025. In 2025, 92.8% of coinfected cases with loiasis hypermicrofilaremia are predicted to live in hypoendemic areas currently not targeted for MDA. Conclusions : Loiasis coinfection is a major concern for onchocerciasis elimination in Africa. We predict that under current strategies, at least 31 000 coinfected people still require treatment for onchocerciasis in 2025 while being at risk of SAEs, justifying continued efforts in research and development for safer drugs and control strategies.

The Onchocerca ochengi adult implant and Brugia malayi microfilariemic Severe-Combined Immunodeficient (SCID) mouse models are validated screens to measure macrofilaricidal and microfilaricidal activities of candidate onchocerciasis drugs. The purpose of this study was to assess whether 5 daily sub-cutaneous (s.c.) injections of standard flubendazole (FBZ) suspension (10mg/kg), a single s.c. injection (10mg/kg) or 5 daily repeated oral doses of FBZ amorphous solid dispersion (ASD) formulation (0.2, 1.5 or 15mg/kg) mediated macrofilaricidal efficacy against O. ochengi male worms implanted into SCID mice. The direct microfilaricidal activity against circulating B. malayi microfilariae of single dose FBZ ASD formulation (2 or 40 mg/kg) was also evaluated and compared against the standard microfilaricide, ivermectin (IVM). Systemic exposures of FBZ/FBZ metabolites achieved following dosing were measured by pharmacokinetic (PK) bioanalysis. At necropsy, five weeks following start of FBZ SC injections, there were significant reductions in burdens of motile O. ochengi worms following multiple injections (93%) or single injection (82%). Further, significant proportions of mice dosed following multiple injections (5/6; 83%) or single injection (6/10; 60%) were infection negative (drug-cured). In comparison, no significant reduction in recovery of motile adult O. ochengi adult worms was obtained in any multiple-oral dosage group. Single oral-dosed FBZ did not mediate any significant microfilaricidal activity against circulating B. malayi mf at 2 or 7 days compared with >80% efficacy of single dose IVM. In conclusion, multiple oral FBZ formulation doses, whilst achieving substantial bioavailability, do not emulate the efficacy delivered by the parenteral route in vivo against adult O. ochengi. PK analysis determined FBZ efficacy was related to sustained systemic drug levels rather than achievable Cmax. PK modelling predicted that oral FBZ would have to be given at low dose for up to 5 weeks in the mouse model to achieve a matching efficacious exposure profile.

Lymphedema (LE) can have various origins of which one is the infection with filarial worms like Wuchereria bancrofti. A previous study showed that a 6-week treatment with 200 mg doxycycline (DOX) did not only exert macro- and microfilaricidal effects but also improved the lymphedema in lymphatic filariasis[for full text, please go to the a.m. URL], Infektiologie Update 2018; 26. Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG)

Introduction Understanding the number of cases of podoconiosis, its geographical distribution and the population at risk are crucial to estimating the burden of this disease in endemic countries. We assessed each of these using nationwide data on podoconiosis prevalence in Cameroon. Methods We analysed data arising from two crosssectional surveys in Cameroon. The dataset was combined with a suite of environmental and climate data and analysed within a robust statistical framework, which included machine learning-based approaches and geostatistical modelling. The environmental limits, spatial variation of predicted prevalence, population at risk and number of cases of podoconiosis were each estimated. Results A total of 214 729 records of individuals screened for podoconiosis were gathered from 748 communities in all 10 regions of Cameroon. Of these screened individuals, 882 (0.41%; 95% CI 0.38 to 0.44) were living with podoconiosis. High environmental suitability for podoconiosis was predicted in three regions of Cameroon (Adamawa, North West and North). The national population living in areas environmentally suitable for podoconiosis was estimated at 5.2 (95% CI 4.7 to 5.8) million, which corresponds to 22.3% of Cameroon’s population in 2015. Countrywide, in 2015, the number of adults estimated to be suffering from podoconiosis was 41 556 (95% CI, 1170 to 240 993). Four regions (Central, Littoral, North and North West) contributed 61.2% of the cases. Conclusion In Cameroon, podoconiosis is more widely distributed geographically than was initially expected. The number of cases and the population at risk are considerable. Expanding morbidity management and follow-up of cases is of utmost necessity. Promotion of footwear use and regular foot hygiene should be at the forefront of any intervention plan.

Background Onchocerciasis and lymphatic filariasis (LF) are major filarial infections targeted for elimination in most endemic sub-Saharan Africa (SSA) countries by 2020/2025. The current control strategies are built upon community-directed mass administration of ivermectin (CDTI) for onchocerciasis, and ivermectin plus albendazole for LF, with evidence pointing towards the potential for novel drug regimens. When distributing microfilaricides however, considerable care is needed to minimise the risk of severe adverse events (SAEs) in areas that are co-endemic for onchocerciasis or LF and loiasis. This work aims to combine previously published predictive risk maps for onchocerciasis, LF and loiasis to (i) explore the scale of spatial heterogeneity in co-distributions, (ii) delineate target populations for different treatment strategies, and (iii) quantify populations at risk of SAEs across the continent. Methods Geographical co-endemicity of filarial infections prior to the implementation of large-scale mass treatment interventions was analysed by combining a contemporary LF endemicity map with predictive prevalence maps of onchocerciasis and loiasis. Potential treatment strategies were geographically delineated according to the level of co-endemicity and estimated transmission intensity. Results In total, an estimated 251 million people live in areas of LF and/or onchocerciasis transmission in SSA, based on 2015 population estimates. Of these, 96 million live in areas co-endemic for both LF and onchocerciasis, providing opportunities for integrated control programmes, and 83 million live in LF-monoendemic areas potentially targetable for the novel ivermectin-diethylcarbamazine-albendazole (IDA) triple therapy. Only 4% of the at-risk population live in areas co-endemic with high loiasis transmission, representing up to 1.2 million individuals at high risk of experiencing SAEs if treated with ivermectin. In these areas, alternative treatment strategies should be explored, including biannual albendazole monotherapy for LF (1.4 million individuals) and ‘test-and-treat’ strategies (8.7 million individuals) for onchocerciasis. Conclusions These maps are intended to initiate discussion around the potential for tailored treatment strategies, and highlight populations at risk of SAEs. Further work is required to test and refine strategies in programmatic settings, providing the empirical evidence needed to guide efforts towards the 2020/2025 goals and beyond.

Background. Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated. Methods. We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination. Results. Areas with 40%-50% precontrol microfilarial prevalence and >= 10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%-80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control. Conclusions. Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful.

Newcastle disease (ND) is one of the major constraints to poultry in most developing countries. It is a highly contagious and fatal disease caused by a virus of the family Paramyxoviridae. In other to evaluate the evidence of ND among village chicken, an epidemiological survey was carried out between September and October 2013 in 7 villages (Foumban, Bangang, Tole, Tiko, Muyuka and Muea) of two regions (West and South-West) in Cameroon. One hundred and thirty (130) blood samples were collected from the wing vein on free range local chicken. The blood was allow to clot at room temperature and the serum collected was kept in a freezer until analysis. Serological tests were done using the indirect ELISA test.The overall seroprevalence was 32.30%, with 28.26 and 34.52% respectively for the West and South-West regions. In the West region, Foumban recorded the highest seroprevalence (34.37%) compared to Bangang (14.29%) while in the South-West region Tole has the highest seroprevalence (70%) followed in order by Tiko (38,7%), Muyuka (30%) and Muea (21,21%). Younger chickens (0-16 weeks) presented a lower seroprevalence (15.38%) than older ones (43.10%). Also, the mean antibody titer was lower in younger chickens (4782.92 unit/ml) than in older hens (7284.88units/ml). Considering the chicken phenotype, naked neck recorded the highest seroprevalence (40%) followed by the normal feathering chicken (38%), the crested (31.82%), the feathered tarsus (27.78%) and finally the crested-feathered tarsus (25%). The seroprevalence of Newcastle disease was not influenced by the vaccination as in the contrary of antibody titer.Keywords: epidemiology, Newcastle disease, local chicken, Cameroon

Background The detailed assessment of nematode activity and viability still remains a relatively undeveloped area of biological and medical research. Computer-based approaches to assessing the motility of larger nematode stages have been developed, yet these lack the capability to detect and analyze the more subtle and important characteristics of the motion of nematodes. There is currently a need to improved methods of assessing the viability and health of parasitic worms. Methods We describe here a system that converts the motion of nematodes through a light-scattering system into an electrical waveform, and allows for reproducible, and wholly non-subjective, assessment of alterations in motion, as well as estimation of the number of nematode worms of different forms and sizes. Here we have used Brugia sp. microfilariae (L1), infective larvae (L3) and adults, together with the free-living nematode Caenorhabditis elegans. Results The motion of worms in a small (200ul) volume can be detected, with the presence of immotile worms not interfering with the readings at practical levels (up to at least 500 L1 /200ul). Alterations in the frequency of parasite movement following the application of the anti-parasitic drugs, (chloroquine and imatinib); the anti-filarial effect of the latter agent is the first demonstrated here for the first time. This system can also be used to estimate the number of parasites, and shortens the time required to estimate parasites numbers, and eliminates the need for microscopes and trained technicians to provide an estimate of microfilarial sample sizes up to 1000 parasites/ml. Alterations in the form of motion of the worms can also be depicted. Conclusions This new instrument, named a "WiggleTron", offers exciting opportunities to further study nematode biology and to aid drug discovery, as well as contributing to a rapid estimate of parasite numbers in various biological samples.

Malaria is Cameroon's most serious and complex public health problem. Its transmission is usually associated with topography, climate and socio-economic conditions. The problem of the disease is aggravated by changing climate, poverty, and lack of efficient controlling mechanisms. Also, the emergence of new parasite strains, expansion of host range due to human population growth and movement, land use change, increasing vectorial capacity, and deteriorating public health infrastructures contribute to the spread of the disease. Due to climate and ecological diversity, there is apparent variation and instability in the epidemiology of its transmission and prevalence. All age groups are particularly vulnerable to even mild malaria during epidemics. The challenges posed by seasonal changes on malaria prevalence urgently demand re-visiting control measures and policy of urban planning. This paper reviews previous studies on seasonal variations and the prevalence of malaria in Mount Cameroon Region. Generally, seasonal changes from these studies are highly linked to malaria prevalence in the region. We also present in this review new measures that need to be taken to harness existing malaria control measures and evade possible malaria epidemics in the region and Cameroon as a whole. We proposed future studies which involve monitoring and modeling the influence of climate change and land use changes on the malariology indices in the Mount Cameroon Region.Keywords: malaria, prevalence, seasonal variationsJOURNAL OF THE CAMEROON ACADEMY OF SCIENCES Vol. 11 No. 1 (2013)

Health decision-makers working in Africa often need to act for millions of people over large geographical areas on little and uncertain information. Spatial statistical modelling and Bayesian inference have now been used to quantify the uncertainty in the predictions of a regional, environmental risk map for Loa loa ( a map that is currently being used as an essential decision tool by the African Programme for Onchocerciasis Control). The methodology allows the expression of the probability that, given the data, a particular location does or does not exceed a predefined high-risk threshold for which a change in strategy for the delivery of the antihelmintic ivermectin is required.

The microfiladermia of Monanema martini was studied in two natural murid hosts, Lemniscomys striatus and Arvicanthis niloticus, with 137 and 39 rodents respectively inoculated once, twice or several times. Microfilarial densities (mf/mm2) were measured at the ear pinna every three months. Almost all the rodents developed a microfiladermia. When L. striatus rodents were inoculated once with 30, 80, or 400 infective larvae, microfiladermia increased (peaks of 108, 148, 174 mf/mm2 respectively, at six to nine months p.i.); this fits with the fact that, in this filaria-host pair, the number of adult filariae is proportional to the number of inoculated larvae, and remains at a constant level for more than eight months. Nevertheless microfiladermia was limited, especially during the peak, showing the complexity of its regulatory mechanisms. Several low doses over one year, resulting in 145 L3, increased the microfiladermia at the same level than one dose of 400 larvae; the recovery rate of the larvae was reduced but the total number of filariae recovered was increased. A. niloticus, from which the filarial strain originates, showed a much lower microfiladermia than L. striatus (7 mf/mm2 with 80 larvae, at six months p.i.). This was due to a smaller recovery rate of the infective larvae in this host and, overall, to a reduced fertility of the female worms and a shorter lifetime of adult filariae. However, repeated inoculations increased the microfiladermia (32 mf/mm2), due to the constant presence of small numbers of young filariae producing microfilariae. It is to be noted that the two biological systems presented by M. martini in L. striatus and A. niloticus correspond to the two types of ocular pathology described in a recent opthalmological study, chorioretinal atrophy and keratitis respectively.