Genetic diversity of SARS-CoV-2 infections in Ghana from 2020-2021.

The COVID-19 pandemic is one of the fastest evolving pandemics in recent history. As such, the SARS-CoV-2 viral evolution needs to be continuously tracked. This study sequenced 1123 SARS-CoV-2 genomes from patient isolates (121 from arriving travellers and 1002 from communities) to track the molecular evolution and spatio-temporal dynamics of the SARS-CoV-2 variants in Ghana. The data show that initial local transmission was dominated by B.1.1 lineage, but the second wave was overwhelmingly driven by the Alpha variant. Subsequently, an unheralded variant under monitoring, B.1.1.318, dominated transmission from April to June 2021 before being displaced by Delta variants, which were introduced into community transmission in May 2021. Mutational analysis indicated that variants that took hold in Ghana harboured transmission enhancing and immune escape spike substitutions. The observed rapid viral evolution demonstrates the potential for emergence of novel variants with greater mutational fitness as observed in other parts of the world.

Is malaria immunity a possible protection against severe symptoms and outcomes of COVID-19?

Malaria-endemic areas of the world are noted for high morbidity and mortality from malaria. Also noted in these areas is the majority of persons in the population having acquired malaria immunity. Though this acquired malaria immunity does not prevent infection, it resists the multiplication of Plasmodium parasites, restricting disease to merely uncomplicated cases or asymptomatic infections. Does this acquired malaria immunity in endemic areas protect against other diseases, especially outbreak diseases like COVID-19? Does malaria activation of innate immunity resulting in trained or tolerance immunity contribute to protection against COVID-19? In an attempt to answer these questions, this review highlights the components of malaria and viral immunity and explores possible links with immunity against COVID-19. With malaria-endemic areas of the world having a fair share of cases of COVID-19, it is important to direct research in this area to evaluate and harness any benefits of acquired malaria immunity to help mitigate the effects of COVID-19 and any possible future outbreaks. FUNDING: None declared.

Is malaria immunity a possible protection against severe symptoms and outcomes of COVID-19?

Malaria-endemic areas of the world are noted for high morbidity and mortality from malaria. Also noted in these areas is the majority of persons in the population having acquired malaria immunity. Though this acquired malaria immunity does not prevent infection, it resists the multiplication of Plasmodium parasites, restricting disease to merely uncomplicated cases or asymptomatic infections. Does this acquired malaria immunity in endemic areas protect against other diseases, especially outbreak diseases like COVID-19? Does malaria activation of innate immunity resulting in trained or tolerance immunity contribute to protection against COVID-19? In an attempt to answer these questions, this review highlights the components of malaria and viral immunity and explores possible links with immunity against COVID-19. With malaria-endemic areas of the world having a fair share of cases of COVID-19, it is important to direct research in this area to evaluate and harness any benefits of acquired malaria immunity to help mitigate the effects of COVID-19 and any possible future outbreaks

African regional progress and status of the programme to eliminate lymphatic filariasis: 2000-2020.

To eliminate lymphatic filariasis (LF) by 2020, the World Health Organization (WHO) has launched a campaign against the disease. Since the launch in 2000, significant progress has been made to achieve this ambitious goal. In this article we review the progress and status of the LF programme in Africa through the WHO neglected tropical diseases preventive chemotherapy databank, the Expanded Special Project for Elimination of Neglected Tropical Diseases (ESPEN) portal and other publications. In the African Region there are 35 countries endemic for LF. The Gambia was reclassified as not requiring preventive chemotherapy in 2015, while Togo and Malawi eliminated LF as a public health problem in 2017 and 2020, respectively. Cameroon discontinued mass drug administration (MDA) and transitioned to post-MDA surveillance to validate elimination. The trajectory of coverage continues to accelerate; treatment coverage increased from 0.1% in 2000 to 62.1% in 2018. Geographical coverage has also significantly increased, from 62.7% in 2015 to 78.5% in 2018. In 2019, 23 of 31 countries requiring MDA achieved 100% geographic coverage. Although much remains to be done, morbidity management and disability prevention services have steadily increased in recent years. Vector control interventions conducted by other programmes, particularly malaria vector control, have had a profound effect in stopping transmission in some endemic countries in the region. In conclusion, significant progress has been made in the LF programme in the region while we identify the key remaining challenges in achieving an Africa free of LF.

Progress towards lymphatic filariasis elimination in Ghana from 2000-2016: Analysis of microfilaria prevalence data from 430 communities.

BACKGROUND: Ghana started its national programme to eliminate lymphatic filariasis (LF) in 2000, with mass drug administration (MDA) with ivermectin and albendazole as main strategy. We review the progress towards elimination that was made by 2016 for all endemic districts of Ghana and analyze microfilaria (mf) prevalence from sentinel and spot-check sites in endemic districts. METHODS: We reviewed district level data on the history of MDA and outcomes of transmission assessment surveys (TAS). We further collated and analyzed mf prevalence data from sentinel and spot-check sites. RESULTS: MDA was initiated in 2001-2006 in all 98 endemic districts; by the end of 2016, 81 had stopped MDA after passing TAS and after an average of 11 rounds of treatment (range 8-14 rounds). The median reported coverage for the communities was 77-80%. Mf prevalence survey data were available for 430 communities from 78/98 endemic districts. Baseline mf prevalence data were available for 53 communities, with an average mf prevalence of 8.7% (0-45.7%). Repeated measurements were available for 78 communities, showing a steep decrease in mean mf prevalence in the first few years of MDA, followed by a gradual further decline. In the 2013 and 2014 surveys, 7 and 10 communities respectively were identified with mf prevalence still above 1% (maximum 5.6%). Fifteen of the communities above threshold are all within districts where MDA was still ongoing by 2016. CONCLUSIONS: The MDA programme of the Ghana Health Services has reduced mf prevalence in sentinel sites below the 1% threshold in 81/98 endemic districts in Ghana, yet 15 communities within 13 districts (MDA ongoing by 2016) had higher prevalence than this threshold during the surveys in 2013 and 2014. These districts may need to intensify interventions to achieve the WHO 2020 target.

Elimination of lymphatic filariasis: current perspectives on mass drug administration.

Following the London declaration on neglected tropical diseases (NTDs) in 2012 and inspired by the WHO 2020 roadmap to control or eliminate NTDs, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) intensified preventive chemotherapy and management of morbidity as the two main strategies to enhance progress towards the elimination of lymphatic filariasis (LF). This paper focuses on current perspectives of mass drug administration (MDA) towards the elimination of LF. The goal of MDA is to reduce the density of parasites circulating in the blood of infected persons and the intensity of infection in communities to levels where transmission is no longer sustainable by the mosquito vector. Three drugs, diethylcarbamazine, albendazole, and ivermectin are currently available for LF treatment, and their effectiveness and relative safety have opened the possibility of treating the entire population at risk. Currently, almost all LF endemic countries rely on the single-dose two-drug regimen recommended by the GPELF to achieve elimination. The 4th WHO report on NTDs has indicated that considerable progress has been made towards elimination of LF in some countries while acknowledging some challenges. In this review, we conclude that the 2020 elimination goal can be achieved if issues pertaining to the drug distribution, health system and implementation challenges are addressed.

Development of a theory and evidence-based program to promote community treatment of fevers in children under five in a rural district in Southern Ghana: An intervention mapping approach.

BACKGROUND: This paper describes the development and implementation of a program to promote prompt and appropriate care seeking for fever in children under the age of five. Designed as a multicomponent program, the intervention comprises elements to influence the behavior of caregivers of children, Community Health Workers, professional health care providers and the wider community. METHODS: Following the six fundamental steps of the Intervention Mapping protocol, we involved relevant stakeholders from the commencement of planning to program end. The IM protocol also recommends various behavior change methods to guide intervention development. RESULTS: The intervention components implemented were successful in achieving program goals. For example, the intervention resulted in the primary outcome of reductions in all-cause mortality of 30% and 44%, among children treated with an antimalarial and those treated with the antimalarial plus an antibiotic respectively. Most Community Health Workers were retained on the program, with an attrition rate of 21.2% over a period of 30 months and the Community Health Workers rate of adherence to performance guidelines was high at 94.6%. CONCLUSION: We were able to systematically develop a theory- and evidence-based health promotion program based on the Intervention Mapping protocol. This article contributes to the response to recent calls for a more detailed description of the development of interventions and trials. The intervention mapping approach can serve as a guide for others interested in developing community- based health interventions in similar settings.

Extent of Integration of Priority Interventions into General Health Systems: A Case Study of Neglected Tropical Diseases Programme in the Western Region of Ghana.

BACKGROUND: The global health system has a large arsenal of interventions, medical products and technologies to address current global health challenges. However, identifying the most effective and efficient strategies to deliver these resources to where they are most needed has been a challenge. Targeted and integrated interventions have been the main delivery strategies. However, the health system discourse increasingly favours integrated strategies in the context of functionally merging targeted interventions with multifunctional health care delivery systems with a focus on strengthening country health systems to deliver needed interventions. Neglected Tropical Diseases (NTD) have been identified to promote and perpetuate poverty hence there has been global effort to combat these diseases. The Neglected Tropical Diseases Programme (NTDP) in Ghana has a national programme team and office, however, it depends on the multifunctional health delivery system at the regional and district level to implement interventions. The NTDP seeks further health system integration to accelerate achievement of coverage targets. The study estimated the extent of integration of the NTDP at the national, regional and district levels to provide evidence to guide further integration. METHODOLOGY/PRINCIPAL FINDINGS: The research design was a descriptive case study that interviewed key persons involved in the programme at the three levels of the health system as well as extensive document review. Integration was assessed on two planes-across health system functions-stewardship and governance, financing, planning, service delivery, monitoring and evaluation and demand generation; and across three administrative levels of the health system-national, regional and district. A composite measure of integration designated Cumulative Integration Index (CII) with a range of 0.00-1.00 was used to estimate extent of integration at the three levels of the health system. Service delivery was most integrated while financing and planning were least integrated. Extent of integration was partial at all levels of the health system with a CII of 0.48-0.68; however it was higher at the district compared to the national and regional levels. CONCLUSIONS/SIGNIFICANCE: To ensure further integration of the NTDP, planning and finance management activities must be decentralized to involve regional and district levels of the health system. The study provides an empirical measure of extent of integration and indicators to guide further integration.

Modelling the distribution and transmission intensity of lymphatic filariasis in sub-Saharan Africa prior to scaling up interventions: integrated use of geostatistical and mathematical modelling.

BACKGROUND: Lymphatic filariasis (LF) is one of the neglected tropical diseases targeted for global elimination. The ability to interrupt transmission is, partly, influenced by the underlying intensity of transmission and its geographical variation. This information can also help guide the design of targeted surveillance activities. The present study uses a combination of geostatistical and mathematical modelling to predict the prevalence and transmission intensity of LF prior to the implementation of large-scale control in sub-Saharan Africa. METHODS: A systematic search of the literature was undertaken to identify surveys on the prevalence of Wuchereria bancrofti microfilaraemia (mf), based on blood smears, and on the prevalence of antigenaemia, based on the use of an immuno-chromatographic card test (ICT). Using a suite of environmental and demographic data, spatiotemporal multivariate models were fitted separately for mf prevalence and ICT-based prevalence within a Bayesian framework and used to make predictions for non-sampled areas. Maps of the dominant vector species of LF were also developed. The maps of predicted prevalence and vector distribution were linked to mathematical models of the transmission dynamics of LF to infer the intensity of transmission, quantified by the basic reproductive number (R0). RESULTS: The literature search identified 1267 surveys that provide suitable data on the prevalence of mf and 2817 surveys that report the prevalence of antigenaemia. Distinct spatial predictions arose from the models for mf prevalence and ICT-based prevalence, with a wider geographical distribution when using ICT-based data. The vector distribution maps demonstrated the spatial variation of LF vector species. Mathematical modelling showed that the reproduction number (R0) estimates vary from 2.7 to 30, with large variations between and within regions. CONCLUSIONS: LF transmission is highly heterogeneous, and the developed maps can help guide intervention, monitoring and surveillance strategies as countries progress towards LF elimination.

Evaluation of human and mosquito based diagnostic tools for defining endpoints for elimination of Anopheles transmitted lymphatic filariasis in Ghana.

BACKGROUND: The decision to stop mass drug administration (MDA) and monitor recrudescence has to be made when endpoints for elimination of lymphatic filariasis (LF) have been achieved. Highly sensitive and specific diagnostic tools are required to do this. The main objective of this study was to determine most effective diagnostic tools for assessing interruption of LF transmission. METHODS: The presence of filarial infection in blood and mosquito samples was determined using five diagnostic tools: Brugia malayi-14 (BM14) antibody detection ELISA, Onchocerca gibsoni antigen (Og4C3) based ELISA, PCR, immunochromatography (ICT) card test and blood smear. The study was carried out in two communities in the Central Region of Ghana. RESULTS: OG4C3 was found to be the most sensitive test but ICT, the second most sensitive, was the most field applicable. PCR was found to be the most specific. Thirteen out of 30 pools of anopheles mosquitoes tested positive for the DNA of Wuchereria bancrofti. CONCLUSIONS: Very low antigen prevalence in primary school children indicates that MDA is working, so children born since the intervention was put in place are not getting infected. Inclusion of xenomonitoring in monitoring the effectiveness of MDA will give a better indication as to when transmission has been interrupted especially in areas where microfilaria prevalence is lower than 1%.

Factors related to retention of community health workers in a trial on community-based management of fever in children under 5 years in the Dangme West District of Ghana.

BACKGROUND: In resource-constrained settings of developing countries, promotion of community-based health interventions through community health workers (CHWs) is an important strategy to improve child health. However, there are concerns about the sustainability of such programmes owing to the high rate of CHW attrition. This study examined factors influencing retention of volunteer CHWs in a cluster randomised trial on community management of under-5 fever in a rural Ghanaian district. METHODS: Data were obtained from structured interviews (n=520) and focus group discussions (n=5) with CHWs. Factors influencing CHWs' decisions to remain or leave the programme were analysed using a probit model, and focus group discussion results were used to elucidate the findings. RESULTS: The attrition rate among CHWs was 21.2%. Attrition was comparatively higher in younger age groups (25.9% in 15-25 years group, 18.2% in 26-45 years group and 16.5% in ≥46 years group). Approval of a CHW by the community (p<0.001) and the CHW's immediate family (p<0.05) were significant in influencing the probability of remaining in the programme. Motivation for retention was related to the desire to serve their communities as well as humanitarian and religious reasons. CONCLUSION: The relatively moderate rate of attrition could be attributed to the high level of community involvement in the selection process as well as other aspects of the intervention leading to high community approval and support. Attention for these aspects could help improve CHW retention in community-based health interventions in Ghana, and the lessons could be applied to countries within similar settings.

Assessment of the adherence of community health workers to dosing and referral guidelines for the management of fever in children under 5 years: a study in Dangme West District, Ghana.

BACKGROUND: Community health workers (CHW) manage simple childhood illnesses in many developing countries. Information on CHWs' referral practices is limited. As part of a large cluster-randomised trial, this study assessed CHWs' adherence to dosing and referral guidelines. METHODS: Records of consultations of children aged 2-59 months with fever managed by CHWs were analysed. Appropriate use of drugs was defined as provision of the correct drug pack(s) for the child's age group. Symptoms requiring referral were categorised into danger signs, respiratory distress and symptoms indicating other illnesses. Multivariate logistic regression examined symptoms most likely to be noted as requiring referral and those associated with provision of a written referral. RESULTS: Most children (11 659/12 330; 94.6%) received the appropriate drug. Only 161 of 1758 (9.2%) children who, according to the guidelines required referral were provided with a written referral. Not drinking/breastfeeding, persistent vomiting, unconsciousness/lethargy, difficultly breathing, fast breathing, bloody stool, sunken eyes and pallor were symptoms significantly associated with being identified by CHWs as needing referral or receiving a written referral. CONCLUSIONS: CHWs' adherence to dosing guidelines was high. Adherence to referral guidelines was inadequate. More effort needs to be put into strengthening referral practices of CHWs within comparable community programmes.

Impact of treating young children with antimalarials with or without antibiotics on morbidity: a cluster-randomized controlled trial in Ghana.

BACKGROUND: Community health workers in Dangme-West district, Ghana, treated children aged 2-59 months with fever with either artesunate-amodiaquine (AAQ) or AAQ plus amoxicillin (AAQ + AMX) within a cluster-randomized controlled trial (registration no. TDR/UNDP Trial registration A: 20189). The intervention was introduced in a stepped-wedge manner. The aim of the study was reduction of mortality. This paper reports on the reduction of morbidity, notably anaemia, severe anaemia and severe illness. Clusters of 100 children were randomized in to AAQ, AAQ + AMX and pre-intervention arms. Six months later the pre-intervention clusters were randomized in to the AAQ and AAQ + AMX arms. METHODS: Data were collected in eight cross-sectional surveys. Using stratified sampling, 10 clusters were randomly selected per survey. Blood samples were taken to assess haemoglobin. Caregivers were interviewed about diseases (signs and symptoms) among their children in the preceding 14 days. Multivariate logistic regression analysis was used to determine the impact on anaemia, severe anaemia and severe illness. RESULTS: Compared with the pre-intervention clusters, anaemia was reduced in the AAQ (OR = 0.20, 95% CI 0.12-0.33) and AAQ + AMX (OR = 0.23, 95% CI 0.15-0.36) clusters, severe anaemia was reduced in the AAQ (OR = 0.20, 95% CI 0.09-0.45) and AAQ + AMX (OR = 0.12, 95% CI 0.04-0.31) clusters and severe illness was reduced in the AAQ (OR = 0.46, 95% CI 0.26-0.80) and AAQ + AMX (OR = 0.38, 95% CI 0.22-0.63) clusters. No significant differences were found in outcome variables between the AAQ and AAQ + AMX clusters. CONCLUSIONS: Treating fever with antimalarials significantly reduced the prevalence of anaemia, severe anaemia and severe illness. We found no significant reduction in outcomes when the AAQ and AAQ+AMX clusters were compared.

Profile: the Dodowa HDSS.

The Dodowa Health and Demographic Surveillance System (DHDSS) operates in the south-eastern part of Ghana. It was established in 2005 after an initial attempt in 2003 by the Dodowa Health Research Centre (DHRC) to have an accurate population base for piloting a community health insurance scheme. As at 2010, the DHDSS had registered 111 976 residents in 22 767 households. The district is fairly rural, with scattered settlements. Information on pregnancies, births, deaths, migration and marriages using household registration books administered by trained fieldworkers is obtained biannually. Education, immunization status and household socioeconomic measures are obtained annually and verbal autopsies (VA) are conducted on all deaths. Community key informants (CKI) complement the work of field staff by notifying the field office of events that occur after a fieldworker has left a community. The centre has very close working relationships with the district health directorate and the local government authority. The DHDSS subscribes to the INDEPTH data-sharing policy and in addition, contractual arrangements are made with various institutions on specific data-sharing issues.

Impact of community management of fever (using antimalarials with or without antibiotics) on childhood mortality: a cluster-randomized controlled trial in Ghana.

Malaria and pneumonia are leading causes of childhood mortality. Home Management of fever as Malaria (HMM) enables presumptive treatment with antimalarial drugs but excludes pneumonia. We aimed to evaluate the impact of adding an antibiotic, amoxicillin (AMX) to an antimalarial, artesunate amodiaquine (AAQ + AMX) for treating fever among children 2-59 months of age within the HMM strategy on all-cause mortality. In a stepped-wedge cluster-randomized, open trial, children 2-59 months of age with fever treated with AAQ or AAQ + AMX within HMM were compared with standard care. Mortality reduced significantly by 30% (rate ratio [RR] = 0.70, 95% confidence interval [CI] = 0.53-0.92, P = 0.011) in AAQ clusters and by 44% (RR = 0.56, 95% CI = 0.41-0.76, P = 0.011) in AAQ + AMX clusters compared with control clusters. The 21% mortality reduction between AAQ and AAQ + AMX (RR = 0.79, 95% CI = 0.56-1.12, P = 0.195) was however not statistically significant. Community fever management with antimalarials significantly reduces under-five mortality. Given the lower mortality trend, adding an antibiotic is more beneficial.

Is home management of fevers a cost-effective way of reducing under-five mortality in Africa? The case of a rural Ghanaian District.

OBJECTIVE: To assess the cost-effectiveness of two strategies of home management of under-five fevers in Ghana - treatment using antimalarials only (artesunate-amodiaquine - AAQ) and combined treatment using antimalarials and antibiotics (artesunate-amodiaquine plus amoxicillin - AAQ + AMX). METHODS: We assessed the costs and cost-effectiveness of AAQ and AAQ + AMX compared with a control receiving standard care. Data were collected as part of a cluster randomised controlled trial with a step-wedged design. Approximately, 12,000 children aged 2-59 months in Dangme West District in southern Ghana were covered. Community health workers delivered the interventions. Costs were analysed from societal perspective, using anaemia cases averted, under-five deaths averted and disability-adjusted life years (DALYs) averted as effectiveness measures. RESULTS: Total economic costs for the interventions were US$ 204,394.72 (AAQ) and US$ 260,931.49 (AAQ + AMX). Recurrent costs constituted 89% and 90% of the total direct costs of AAQ and AAQ + AMX, respectively. Deaths averted were 79.1 (AAQ) and 79.9 (AAQ + AMX), with DALYs averted being 2264.79 (AAQ) and 2284.57 (AAQ + AMX). The results show that cost per anaemia case averted were US$ 150.18 (AAQ) and US$ 227.49 (AAQ + AMX) and cost per death averted was US$ 2585.58 for AAQ and US$ 3272.20 for AAQ + AMX. Cost per DALY averted were US$ 90.25 (AAQ) and US$ 114.21 (AAQ + AMX). CONCLUSION: Both AAQ and AAQ + AMX approaches were cost-effective, each averting one DALY at less than the standard US$ 150 threshold recommended by the World Health Organisation. However, AAQ was more cost-effective. Home management of under-five fevers in rural settings is cost-effective in reducing under-five mortality.

Genotypic analysis of ß-tubulin in Onchocerca volvulus from communities and individuals showing poor parasitological response to ivermectin treatment.

Ivermectin (IVM) has been in operational use for the control of onchocerciasis for two decades and remains the only drug of choice. To investigate the parasitological responses and genetic profile of Onchocerca volvulus, we carried out a 21 month epidemiological study to determine the response of the parasite to IVM in 10 Ghanaian endemic communities. Onchocerca nodules were surgically removed from patients in three IVM response categories (good, intermediate and poor) and one IVM naïve community. DNA from adult worms was analyzed to determine any association between genotype and IVM response phenotypic. Embryogramme analysis showed significantly higher reproductive activity in worms from poor response communities, which had up to 41% of females with live stretched microfilaria (mf) in utero, despite IVM treatment, compared with good response communities, which had no intra-uterine stretched mf. ß-tubulin isotype 1 gene has been shown to be linked to IVM selection in O. volvulus and also known to be associated with IVM resistance in veterinary nematodes. We have genotyped the full length genomic DNA sequence of the ß-tubulin gene from 127 adult worms obtained from the four community categories. We found SNPs at 24 sites over the entire 3696 bp. Eight of the SNPs occurred at significantly higher (p < 0.05) frequencies in the poor response communities compared with the good response communities and the IVM naïve community. Phenotypic and genotypic analyses show that IVM resistance has been selected and the genotype (1183GG/1188CC/1308TT/1545GG) was strongly associated with the resistance phenotype. Since the region in the ß-tubulin gene where these four SNPs occur is within 362 bp, it is feasible to develop a genetic marker for the early detection of IVM resistance.

Mapping helminth co-infection and co-intensity: geostatistical prediction in ghana.

BACKGROUND: Morbidity due to Schistosoma haematobium and hookworm infections is marked in those with intense co-infections by these parasites. The development of a spatial predictive decision-support tool is crucial for targeting the delivery of integrated mass drug administration (MDA) to those most in need. We investigated the co-distribution of S. haematobium and hookworm infection, plus the spatial overlap of infection intensity of both parasites, in Ghana. The aim was to produce maps to assist the planning and evaluation of national parasitic disease control programs. METHODOLOGY/PRINCIPAL FINDINGS: A national cross-sectional school-based parasitological survey was conducted in Ghana in 2008, using standardized sampling and parasitological methods. Bayesian geostatistical models were built, including a multinomial regression model for S. haematobium and hookworm mono- and co-infections and zero-inflated Poisson regression models for S. haematobium and hookworm infection intensity as measured by egg counts in urine and stool respectively. The resulting infection intensity maps were overlaid to determine the extent of geographical overlap of S. haematobium and hookworm infection intensity. In Ghana, prevalence of S. haematobium mono-infection was 14.4%, hookworm mono-infection was 3.2%, and S. haematobium and hookworm co-infection was 0.7%. Distance to water bodies was negatively associated with S. haematobium and hookworm co-infections, hookworm mono-infections and S. haematobium infection intensity. Land surface temperature was positively associated with hookworm mono-infections and S. haematobium infection intensity. While high-risk (prevalence >10-20%) of co-infection was predicted in an area around Lake Volta, co-intensity was predicted to be highest in foci within that area. CONCLUSIONS/SIGNIFICANCE: Our approach, based on the combination of co-infection and co-intensity maps allows the identification of communities at increased risk of severe morbidity and environmental contamination and provides a platform to evaluate progress of control efforts.

Phenotypic evidence of emerging ivermectin resistance in Onchocerca volvulus.

BACKGROUND: Ivermectin (IVM) has been used in Ghana for over two decades for onchocerciasis control. In recent years there have been reports of persistent microfilaridermias despite multiple treatments. This has necessitated a reexamination of its microfilaricidal and suppressive effects on reproduction in the adult female Onchocerca volvulus. In an initial study, we demonstrated the continued potent microfilaricidal effect of IVM. However, we also found communities in which the skin microfilarial repopulation rates at days 90 and 180 were much higher than expected. In this follow up study we have investigated the reproductive response of female worms to multiple treatments with IVM. METHODS AND FINDINGS: The parasitological responses to IVM in two hundred and sixty-eight microfilaridermic subjects from nine communities that had received 10 to 19 annual doses of IVM treatment and one pre-study IVM-naïve community were followed. Skin snips were taken 364 days after the initial IVM treatment during the study to determine the microfilaria (mf) recovery rate. Nodules were excised and skin snips taken 90 days following a second study IVM treatment. Nodule and worm density and the reproductive status of female worms were determined. On the basis of skin mf repopulation and skin mf recovery rates we defined three categories of response--good, intermediate and poor--and also determined that approximately 25% of subjects in the study carried adult female worms that responded suboptimally to IVM. Stratification of the female worms by morphological age and microfilarial content showed that almost 90% of the worms were older or middle aged and that most of the mf were produced by the middle aged and older worms previously exposed to multiple treatments with little contribution from young worms derived from ongoing transmission. CONCLUSIONS: The results confirm that in some communities adult female worms were non-responsive or resistant to the anti-fecundity effects of multiple treatments with IVM. A scheme of the varied responses of the adult female worm to multiple treatments is proposed.