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Introduction: Act to End NTDs | West, a USAID-funded program that supports national governments to eliminate or control five neglected tropical diseases (NTDs) in West Africa including trachoma, lymphatic filariasis (LF), onchocerciasis, schistosomiasis and soil-transmitted helminthiasis, conducted a gender and social inclusion analysis to determine how NTDs differentially impact various populations and how gender and social norms impact NTD programs to inform future programming. Methods: The study used a mixed methods approach including a literature review; primary qualitative data collection; and monitoring data in Côte d'Ivoire, Sierra Leone, and Ghana. Results: Women and girls face additional health risks from many NTDs compared to men and boys. In addition to differential health burden, the social and economic impacts of NTD-related disability or infertility can be particularly dire for women and girls. Men were somewhat less likely to participate in mass drug administration (MDAs) due to: lack of information about campaigns, lack of access due to work, and higher levels of mistrust of the government and concerns about side effects of the medicines. Pregnant and breastfeeding women were sometimes excluded by community drug distributors (CDDs) from certain types of MDAs for which they are eligible. Training participation rates for CDDs and supervisors were universally higher for men than women, even though feedback on the effectiveness of female CDDs was overwhelmingly positive, and female CDDs often have more access to other women in conservative households. The role of a CDD can lead to career and social opportunities for women. However, challenges faced by CDDs were seen as a greater barrier for women, including transportation, safety, household responsibilities, lower education levels, and low or lack of wages. Discussion: Programs to address NTDs can promote equity and improve programming by increasing women's participation as CDDs and providing financial compensation. Additionally, programs should prioritize inclusive training for CDDs, and inclusive messaging about MDA for communities. Author summary: The Act to End NTDs | West program supports USAID's efforts to control or eliminate trachoma, lymphatic filariasis (LF), onchocerciasis, schistosomiasis and soil-transmitted helminthiasis in 11 West African countries using mass drug administration.Act | West conducted a gender and social inclusion analysis to inform a strategy for the program to improve outcomes and more meaningfully engage and empower women and marginalized individuals in program implementation. Our objective was to identify how gender and social norms and stigma differentially impact men's and women's adoption of healthy practices around NTD prevention, use of NTD services, participation in programing, and opportunities to engage in identifying solutions, using an intersectional lens inclusive of disability, ethnic identity, and geographic location. Several studies have looked at gender dimensions of staffing for NTD programming, analyzed differential risk factors and prevalence of NTDs between males and females, or presented data on gender and national mass drug administration (MDA) coverage to combat NTDs. This paper aims to consolidate these findings through a literature review as well as a qualitative study conducted in Côte d'Ivoire, Ghana, and Sierra Leone, to provide a comprehensive look at gender and social inclusion within NTD programming across various contexts and diseases. This study found that women and girls face additional health risks from five NTDs compared to men and boys. In addition to the health burden, the social and economic impacts of NTD-related disability or infertility can be particularly severe for women and girls. Additionally, men were somewhat less likely to participate in mass drug administration (MDAs) and pregnant and breastfeeding women were sometimes excluded by community drug distributors (CDDs) from certain types of MDAs for which they are eligible due to misunderstanding on the part of CDDs and community members on eligibility criteria. Training participation rates for CDDs and supervisors were universally higher for men than women, even though feedback on the effectiveness of female CDDs was overwhelmingly positive, and female CDDs often have more access to other women in conservative households. Additionally, challenges faced by CDDs were seen as a greater barrier for women to serve in that capacity. [ABSTRACT FROM AUTHOR]

Background: Moxidectin is a macrocyclic lactone registered for the treatment of human onchocerciasis. The drug has a good safety profile, large volume of distribution and a long elimination half-life. This paper reports tolerability data from the first use of moxidectin in persons with Wuchereria bancrofti infection. Methods: In this randomized, open-label, masked-observer superiority trial, adults with Wuchereria bancrofti microfilaremia in Côte d'Ivoire were randomized to 1 of 4 treatment arms: ivermectin + albendazole (IA), moxidectin + albendazole (MoxA), ivermectin + diethylcarbamazine (DEC) + albendazole (IDA), or moxidectin + DEC + albendazole (MoxDA). As part of a larger efficacy trial, all participants were closely monitored for 7 days after treatment. Results: One hundred sixty-four individuals were treated, and monitored for treatment emergent adverse events (TEAE). Eighty-seven participants (53%) experienced one or more mild (grade 1) or moderate (grade 2) TEAE. Four participants had transient Grade 3 hematuria after treatment (3 after IDA and 1 after IA). There were no serious adverse events. There were no significant differences in frequency or types of TEAE between treatment groups (IA = 22/41 (53%), MoxA = 24/40 (60%), IDA = 18/41 (44%), MoxDA = 15/42 (36%), p = 0.530). Fifty-nine participants (36%) had multiple TEAE, and 8.5% had a one or more grade 2 (moderate) TEAE. Grade 2 TEAE were more frequent after triple drug treatments (IDA, 14.6%; MoxDA, 9.5%) than after two-drug treatments (IA, 7.3%; MoxA, 2.5%). There was no difference in TEAEs based on baseline Mf counts (OR 0.69 (0.33, 1.43), p-value 0.319). Conclusion: All treatment regimens were well tolerated. We observed no difference in safety parameters between regimens that contained ivermectin or moxidectin. Trial registration: Clinicaltrials.gov, NCT04410406. Author summary: Lymphatic Filariasis (LF) is a mosquito-borne parasitic infection caused predominantly by Wuchereria bancrofti. Infection can lead to significant lymphatic dysfunction, including hydroceles and lymphedema, which can progress to elephantiasis. The World Health Organization's Global Programme to Eliminate LF (GPELF) recommends mass drug administration (MDA) in endemic populations to eliminate the disease. GPELF recommendations for MDA include ivermectin (IVM) plus albendazole (IA) in sub-Saharan Africa where onchocerciasis is present. In 2018 the US Food and Drug Administration approved use of moxidectin for treatment of onchocerciasis. Moxidectin is a macrocytic lactone, similar to IVM, but more lipophilic, with a larger volume of distribution and longer half-life. Onchocerciasis studies found moxidectin to be superior to IVM for clearance of microfiladermia in people with onchocerciasis, with a treatment emergent adverse event (TEAE) profile similar to that of ivermectin. Moxidectin has not yet been studied, alone or in combination with other antihelminthic drugs. This is a safety evaluation of the first trial of moxidectin combination therapy for LF, which shows that moxidectin combination regimens are well tolerated in Wuchereria bancrofti-infected patients, with a TEAE profile comparable to standard ivermectin containing regimens. [ABSTRACT FROM AUTHOR]

Background: Work to control the gambiense form of human African trypanosomiasis (gHAT), or sleeping sickness, is now directed towards ending transmission of the parasite by 2030. In order to supplement gHAT case-finding and treatment, since 2011 tsetse control has been implemented using Tiny Targets in a number of gHAT foci. As this intervention is extended to new foci, it is vital to understand the costs involved. Costs have already been analysed for the foci of Arua in Uganda and Mandoul in Chad. This paper examines the costs of controlling Glossina palpalis palpalis in the focus of Bonon in Côte d'Ivoire from 2016 to 2017. Methodology/Principal findings: Some 2000 targets were placed throughout the main gHAT transmission area of 130 km2 at a density of 14.9 per km2. The average annual cost was USD 0.5 per person protected, USD 31.6 per target deployed of which 12% was the cost of the target itself, or USD 471.2 per km2 protected. Broken down by activity, 54% was for deployment and maintenance of targets, 34% for tsetse surveys/monitoring and 12% for sensitising populations. Conclusions/Significance: The cost of tsetse control per km2 of the gHAT focus protected in Bonon was more expensive than in Chad or Uganda, while the cost per km2 treated, that is the area where the targets were actually deployed, was cheaper. Per person protected, the Bonon cost fell between the two, with Uganda cheaper and Chad more expensive. In Bonon, targets were deployed throughout the protected area, because G. p. palpalis was present everywhere, whereas in Chad and Uganda G. fuscipes fuscipes was found only the riverine fringing vegetation. Thus, differences between gHAT foci, in terms of tsetse ecology and human geography, impact on the cost-effectiveness of tsetse control. It also demonstrates the need to take into account both the area treated and protected alongside other impact indicators, such as the cost per person protected. Author summary: Sleeping sickness is a fatal disease in Africa caused by trypanosomes transmitted by the bite of infected tsetse flies. The World Health Organization has set the absence of new infections as a goal for 2030. To achieve this, screening and treatment of patients is supplemented by tsetse control. Tiny Targets are small insecticide-impregnated panels of blue cloth and black netting which attract and kill tsetse. To maintain the momentum in these last stages of eliminating the disease, it is important to understand the costs of vector control. This paper presents the results of two years' cost monitoring in Bonon, an area covering 130 km2, home to 120,000 people. Since 2016, ~2,000 Tiny Targets have been deployed annually at a cost of USD 471 per km2 per year. Bonon is a degraded forested area and a relatively high number of targets was required as tsetse are present throughout. Nevertheless, the cost comes to only USD 0.5 per person protected per year. Compared to operations using Tiny Targets in Uganda and Chad, the cost was higher per km2 protected, reflecting the need to place targets throughout the area, but low per person protected compared to Chad, highlighting the need to use a range of comparators. [ABSTRACT FROM AUTHOR]

Mathematical models of vector-borne infections, including malaria, often assume age-independent mortality rates of vectors, despite evidence that many insects senesce. In this study we present survival data on insecticide-resistant Anopheles gambiae s.l. from experiments in Côte d'Ivoire. We fit a constant mortality function and two age-dependent functions (logistic and Gompertz) to the data from mosquitoes exposed (treated) and not exposed (control) to insecticide-treated nets (ITNs), to establish biologically realistic survival functions. This enables us to explore the effects of insecticide exposure on mosquito mortality rates, and the extent to which insecticide resistance might impact the effectiveness of ITNs. We investigate this by calculating the expected number of infectious bites a mosquito will take in its lifetime, and by extension the vectorial capacity. Our results show that the predicted vectorial capacity is substantially lower in mosquitoes exposed to ITNs, despite the mosquitoes in the experiment being highly insecticide-resistant. The more realistic age-dependent functions provide a better fit to the experimental data compared to a constant mortality function and, hence, influence the predicted impact of ITNs on malaria transmission potential. In models with age-independent mortality, there is a great reduction for the vectorial capacity under exposure compared to no exposure. However, the two age-dependent functions predicted an even larger reduction due to exposure, highlighting the impact of incorporating age in the mortality rates. These results further show that multiple exposures to ITNs had a considerable effect on the vectorial capacity. Overall, the study highlights the importance of including age dependency in mathematical models of vector-borne disease transmission and in fully understanding the impact of interventions. Author summary: Interventions against malaria are most commonly targeted on the adult mosquitoes, which transmit the infection from person to person. One of the most important interventions are bed-nets, treated with insecticides. Unfortunately, extensive exposure of mosquitoes to insecticide has led to widespread evolution of insecticide resistance, which might threaten control strategies. Piecing together the overall impact of resistance on the efficacy of insecticide-treated nets is complex, but can be informed by the use of mathematical models. However, there are some assumptions that the models frequently use which are not realistic in terms of the mosquito biology. In this paper, we formulate a model that includes age-dependent mortality rates, an important parameter in vector control since control strategies most commonly aim to reduce the lifespan of the mosquitoes. By using novel data collected using field-derived insecticide-resistant mosquitoes, we explore the effects that the presence of insecticides on nets have on the mortality rates, as well as the difference incorporating age dependency in the model has on the results. We find that including age-dependent mortality greatly alters the anticipated effects of insecticide-treated nets on mosquito transmission potential, and that ignoring this realism potentially overestimates the negative impact of insecticide resistance. [ABSTRACT FROM AUTHOR]

Background: Onchocerciasis control in Côte d’Ivoire started with aerial insecticide spraying in 1974 and continued with community directed treatment with ivermectin (CDTi) from 1992 to the present. Onchocerciasis and lymphatic filariasis (LF) are co-endemic in 46 of the 81 health districts in the country. Fourteen and 12 districts are endemic for only LF or onchocerciasis, respectively. This paper aims to review the impact of past interventions on onchocerciasis in Côte d’Ivoire between 1975 and 2013, and review plans for disease elimination. Methods: We reviewed microfilaria (MF, skin snip) prevalence and community microfilarial load (CMFL) data from published reports from 53 health districts during two major epidemiological assessment periods. Data from 1975 through 1991 provided information on the impact of vector control, and data from 1992 through 2016 provided information on the impact of CDTi. Results: Weekly aerial insecticide spraying in 8 endemic districts between 1975 and 1991 reduced the overall MF prevalence by 68.1% from 43.5% to 13.9%. The CMFL also decreased in 7 out of 8 surveyed communities by 95.2% from 9.24 MF/snip to 0.44 MF/snip. Ivermectin distribution started in 1992. The coverage targets for control (65% of the total population) was reached in most endemic districts, and some areas achieved 80% coverage. Two sets of surveys were conducted to assess the impact of CDTi. Results from the first repeat surveys showed a significant decrease in overall MF prevalence (by 75.7%, from 41.6% to 10.1%). The second follow-up evaluation showed further improvement in most endemic districts and also documented major reductions in CMFL compared to baseline. Conclusions: Extensive data collected over many years document the very significant impact of interventions conducted by the National Onchocerciasis and other Eyes Diseases Control Programme during challenging times with periods of civil unrest. The Health Ministry has now integrated efforts to control neglected tropical diseases and adopted the goal of onchocerciasis elimination. [ABSTRACT FROM AUTHOR]

Insecticide resistance in Anopheles mosquitoes is seriously threatening the success of insecticide-based malaria vector control. Surveillance of insecticide resistance in mosquito populations and identifying the underlying mechanisms enables optimisation of vector control strategies. Here, we investigated the molecular mechanisms of insecticide resistance in three Anopheles coluzzii field populations from southern Côte d'Ivoire, including Agboville, Dabou and Tiassalé. All three populations were resistant to bendiocarb, deltamethrin and DDT, but not or only very weakly resistant to malathion. The absence of malathion resistance is an unexpected result because we found the acetylcholinesterase mutation Ace1-G280S at high frequencies, which would typically confer cross-resistance to carbamates and organophosphates, including malathion. Notably, Tiassalé was the most susceptible population to malathion while being the most resistant one to the pyrethroid deltamethrin. The resistance ratio to deltamethrin between Tiassalé and the laboratory reference colony was 1,800 fold. By sequencing the transcriptome of individual mosquitoes, we found numerous cytochrome P450-dependent monooxygenases – including CYP6M2, CYP6P2, CYP6P3, CYP6P4 and CYP6P5 – overexpressed in all three field populations. This could be an indication for negative cross-resistance caused by overexpression of pyrethroid-detoxifying cytochrome P450s that may activate pro-insecticides, thereby increasing malathion susceptibility. In addition to the P450s, we found several overexpressed carboxylesterases, glutathione S-transferases and other candidates putatively involved in insecticide resistance. Author summary: Insecticide-based mosquito control has saved millions of lives from malaria and other vector-borne diseases. However, the emergence and increase of insecticide resistant Anopheles populations seriously threaten to derail malaria control programmes. Surveillance of insecticide resistance and understanding the underlying molecular mechanisms are key for choosing effective vector control strategies. Here, we characterised the degree and mechanisms of resistance in three malaria vector populations from Côte d'Ivoire. Our key finding was that these multi-insecticide resistant malaria vectors largely remained susceptible to malathion, despite the presence of a mutation in the target enzyme of this organophosphate insecticide that would typically confer resistance. Intriguingly, we found overexpression of metabolic P450 enzymes that are known to detoxify insecticides and activate pro-insecticides such as malathion. It is highly probable that, here, we observed P450-mediated negative cross-resistance for the first time in Anopheles field populations. Negative cross-resistance merits further investigation as advantage could be taken of this phenomenon in the fight against multi-resistant malaria vectors. [ABSTRACT FROM AUTHOR]

Tool use is considered a driving force behind the evolution of brain expansion and prolonged juvenile dependency in the hominin lineage. However, it remains rare across animals, possibly due to inherent constraints related to manual dexterity and cognitive abilities. In our study, we investigated the ontogeny of tool use in chimpanzees (Pan troglodytes), a species known for its extensive and flexible tool use behavior. We observed 70 wild chimpanzees across all ages and analyzed 1,460 stick use events filmed in the Taï National Park, Côte d'Ivoire during the chimpanzee attempts to retrieve high-nutrient, but difficult-to-access, foods. We found that chimpanzees increasingly utilized hand grips employing more than 1 independent digit as they matured. Such hand grips emerged at the age of 2, became predominant and fully functional at the age of 6, and ubiquitous at the age of 15, enhancing task accuracy. Adults adjusted their hand grip based on the specific task at hand, favoring power grips for pounding actions and intermediate grips that combine power and precision, for others. Highly protracted development of suitable actions to acquire hidden (i.e., larvae) compared to non-hidden (i.e., nut kernel) food was evident, with adult skill levels achieved only after 15 years, suggesting a pronounced cognitive learning component to task success. The prolonged time required for cognitive assimilation compared to neuromotor control points to selection pressure favoring the retention of learning capacities into adulthood. Tool use is considered a driving force behind the evolution of brain expansion and prolonged juvenile dependency in the hominin lineage. A study of stick tool use in wild chimpanzees reveals a prolonged time for cognitive assimilation, suggesting selection pressure that favors retention of learning capacities into adulthood. [ABSTRACT FROM AUTHOR]

The supply of drinking water is a vital challenge for the people who live on the African continent, as this continent is experiencing strong demographic growth and therefore increasing water demands. To meet these needs, surface water resources are becoming increasingly mobilized because underground resources are not always available or have already been overexploited. This situation is the case in the region of Abidjan in the Ivory Coast, where the drinking water deficit is a growing problem and it is therefore necessary to mobilize new water resources to ensure the supply of drinking water. Among the potential resources, local managers have identified a freshwater lagoon, Lagoon Aghien, That is in close proximity to the city of Abidjan. With the aim of enhancing knowledge on the ecological functioning of the lagoon and contributing to the assessment of its ability to provide drinking water, several physical and chemical parameters of the water and the phytoplankton community of the lagoon were monitored for 17 months (December 2016-April 2018) at six sampling stations. Our findings show that the lagoon is eutrophic, as evidenced by the high concentrations of total phosphorus (>140 μg L-1), nitrogen (1.36 mg L-1) and average chlorophyll-a (26 to 167 μg L-1) concentrations. The phytoplankton community in the lagoon is dominated by genera typical of eutrophic environments including mixotrophic genera such as Peridinium and by cyanobacteria such as Cylindrospermopsis/Raphidiopsis, Microcystis and Dolichospermum that can potentially produce cyanotoxins. The two rainfall peaks that occur in June and October appeared to be major events in terms of nutrient flows entering the lagoon, and the dynamics of these flows are complex. Significant differences were also found in the nutrient concentrations and to a lesser extent in the phytoplankton communities among the different stations, especially during the rainfall peaks. Overall, these results reveal that the quality of the lagoon's water is already severely degraded, and this degradation could increase in future years due to increasing urbanization in the watershed. These results therefore raise questions about the potential use of the lagoon as a source of drinking water if measures are not taken very quickly to protect this lagoon from increasing eutrophication and other pollution sources. [ABSTRACT FROM AUTHOR]

This qualitative study investigated the effectiveness of blended learning using MOOCs (massive open online courses) for capacity-building in knowledge translation (KT). The evaluation followed Kirkpatrick's updated model. A total of 23 semi-directed interviews were conducted with participants working at a research centre in Côte d'Ivoire, with a first wave of interviews immediately post-training and a second wave after five months. Results showed that the training met learners' needs, with both the content and teaching format being deemed appropriate. Learners reacted positively to face-to-face activities and affirmed the importance of coaching for putting learning into practice. Specific KT skills and principles appeared to have been acquired, such as a procedure for structuring the KT process and improved skills for communicating and presenting scientific knowledge. Five months after the training, encouraging changes were reported, but the sustainability of the new KT practices remained uncertain. KT capacity-building initiatives in low- and middle-income countries struggle to meet demand. Little is known about effective KT training in that context, and even less in non-anglophone countries. The study presented here contributes to the understanding of success factors from the learners' standpoint. [ABSTRACT FROM AUTHOR]

Background: Chronic tropical cutaneous ulcers remain a neglected medical condition in West Africa, particularly Buruli ulcer, which is caused by mycolactone cytotoxin-secreting Mycobacterium ulcerans (M. ulcerans). Medical management of this highly debilitating and necrotising skin infection may be modified by colonisation and co-infection of the ulcer by opportunistic and pathogenic microorganisms, which considerably delays and increases the cost of treatment. Methodology/principal finding: We diagnosed chronic tropical cutaneous ulcers in nine patients in Côte d'Ivoire using M. ulcerans-specific PCRs and culturomics. This revealed M. ulcerans in 7/9 ulcer swabs and 5/9 control swabs as well as an additional 122 bacterial species, 32 of which were specific to ulcers, 61 specifics to the controls, and 29 which were shared, adding 40 bacterial species to those previously reported. Whole genome sequencing of four Bordetella trematum (B. trematum) isolates in four Buruli ulcer swabs and no controls indicated cytolethal distending toxins, as confirmed by cytotoxic assay. Conclusions/significance: In four cases of Buruli ulcer in Côte d'Ivoire, B. trematum was a co-pathogen which was resistant to rifampicin and clarithromycin, unmatching M. ulcerans antibiotic susceptibility profile and counteracting the current treatment of Buruli ulcer in West Africa and Australia. Thus, we report here chronic mixed M. ulcerans-B. trematum chronic tropical ulcer as a specific form of Buruli ulcer in West Africa. Author summary: Buruli ulcer, a severe necrotising skin infection caused by M. ulcerans, remains a neglected health problem in some rural communities in West Africa. Although it can be successfully treated with an antibiotic combination of rifampicin and streptomycin or clarithromycin, the presence of other pathogens or opportunistic agents complicates its management. These co-infections or superinfections make treatment more complex and expensive. In this study, we highlight the association of M. ulcerans, a cytotoxin producer, with B. trematum, another toxin producer associated with chronic ulcers in Buruli ulcer patients. B. trematum shows resistance to the antibiotics used in the Buruli ulcer treatment regimen. Therefore, it is essential to conduct further research to understand the magnitude of its contribution to the illness. [ABSTRACT FROM AUTHOR]

Tactical warfare is considered a driver of the evolution of human cognition. One such tactic, considered unique to humans, is collective use of high elevation in territorial conflicts. This enables early detection of rivals and low-risk maneuvers, based on information gathered. Whether other animals use such tactics is unknown. With a unique dataset of 3 years of simultaneous behavioral and ranging data on 2 neighboring groups of western chimpanzees, from the Taï National Park, Côte d'Ivoire, we tested whether chimpanzees make decisions consistent with tactical use of topography to gain an advantage over rivals. We show that chimpanzees are more likely to use high hills when traveling to, rather than away from, the border where conflict typically takes place. Once on border hills, chimpanzees favor activities that facilitate information gathering about rivals. Upon leaving hills, movement decisions conformed with lowest risk engagement, indicating that higher elevation facilitates the detection of rivals presence or absence. Our results support the idea that elevation use facilitated rival information gathering and appropriate tactical maneuvers. Landscape use during territorial maneuvers in natural contexts suggests chimpanzees seek otherwise inaccessible information to adjust their behavior and points to the use of sophisticated cognitive abilities, commensurate with selection for cognition in species where individuals gain benefits from coordinated territorial defense. We advocate territorial contexts as a key paradigm for unpicking complex animal cognition. Use of high elevation in warfare requires high cognitive skills but is not uniquely human. This study shows that wild chimpanzees can detect their enemies from afar by exploiting hilltops in their topographic landscape, allowing them to assess the risk and adjust their movements accordingly. [ABSTRACT FROM AUTHOR]

Chimpanzees have been used extensively as a model system for laboratory research on infectious diseases. Ironically, we know next to nothing about disease dynamics in wild chimpanzee populations. Here, we analyze long-term demographic and behavioral data from two habituated chimpanzee communities in Taï National Park, Côte d'Ivoire, where previous work has shown respiratory pathogens to be an important source of infant mortality. In this paper we trace the effect of social connectivity on infant mortality dynamics. We focus on social play which, as the primary context of contact between young chimpanzees, may serve as a key venue for pathogen transmission. Infant abundance and mortality rates at Taï cycled regularly and in a way that was not well explained in terms of environmental forcing. Rather, infant mortality cycles appeared to self-organize in response to the ontogeny of social play. Each cycle started when the death of multiple infants in an outbreak synchronized the reproductive cycles of their mothers. A pulse of births predictably arrived about twelve months later, with social connectivity increasing over the following two years as the large birth cohort approached the peak of social play. The high social connectivity at this play peak then appeared to facilitate further outbreaks. Our results provide the first evidence that social play has a strong role in determining chimpanzee disease transmission risk and the first record of chimpanzee disease cycles similar to those seen in human children. They also lend more support to the view that infectious diseases are a major threat to the survival of remaining chimpanzee populations. [ABSTRACT FROM AUTHOR]

Background: Human African trypanosomiasis is a parasitic disease caused by trypanosomes among which Trypanosoma brucei gambiense is responsible for a chronic form (gHAT) in West and Central Africa. Its elimination as a public health problem (EPHP) is being achieved. Côte d'Ivoire was one of the first countries to be validated by WHO in 2020 and this was particularly challenging as the country still reported around a hundred cases a year in the early 2000s. This article describes the strategies implemented including a mathematical model to evaluate the reporting results and infer progress towards sustainable elimination. Methods: The control methods used combined both exhaustive and targeted medical screening strategies including the follow-up of seropositive subjects considered as potential asymptomatic carriers to diagnose and treat cases as well as vector control to reduce the risk of transmission in the most at-risk areas. A mechanistic model was used to estimate the number of underlying infections and the probability of elimination of transmission (EoT) between 2000–2021 in two endemic and two hypo-endemic health districts. Results: Between 2015 and 2019, nine gHAT cases were detected in the two endemic health districts of Bouaflé and Sinfra in which the number of cases/10,000 inhabitants was far below 1, a necessary condition for validating the EPHP. Modelling estimated a slow but steady decline in transmission across the four health districts, bolstered in the two endemic health districts by the introduction of vector control. The decrease in underlying transmission in all health districts corresponds to a high probability that EoT has already occurred in Côte d'Ivoire. Conclusion: This success was achieved through a multi-stakeholder and multidisciplinary one health approach where research has played a major role in adapting tools and strategies to this large epidemiological transition to a very low prevalence. This integrated approach will need to continue to reach the verification of EoT in Côte d'Ivoire targeted by 2025. Author summary: Significant efforts to control Trypanosoma brucei gambiense human African trypanosomiasis (gHAT) have drastically reduced the prevalence of the disease and elimination of transmission (EoT) is targeted for 2030 by WHO. This reduction was particularly challenging in Côte d'Ivoire as it still faced epidemic episodes in the early 2000s. This large epidemiological transition to very low prevalence necessitated the adaptation and evolution of both medical and vector control strategies described in this article. A mathematical model was also used to retrospectively analyse case reporting results, indicating with high probability that local EoT has already been achieved in the four health districts analysed. With nine gHAT cases detected in two health districts between 2015 and 2019 and less than one case per 10,000 people per year in all health districts at national level over this five-year period, Côte d'Ivoire received validation by WHO of achievement of the elimination of the disease as a public health problem in 2020. These results combined with the modelling offer encouragement regarding reaching the verification of EoT targeted by 2025 in Côte d'Ivoire on condition of maintaining such multidisciplinary one health approach including research activities to continuously adapt it to the epidemiological transition to zero incidence. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis and hookworm infection remain public health problems in large parts of sub-Saharan Africa. The epidemiology of schistosomiasis and hookworm was studied in seasonal transmission settings in the northern part of Côte d'Ivoire. Methodology: In August 2018, a cross-sectional study was conducted. Urine and stool samples were collected from 742 individuals aged 6–96 years in 16 localities from four departments in northern Côte d'Ivoire. Urine samples were examined by a filtration method for quantification of Schistosoma haematobium eggs. Stool samples were subjected to duplicate Kato-Katz thick smears and eggs of Schistosoma mansoni and soil-transmitted helminths (STHs) were counted. Additionally, a questionnaire was administered to determine demographic characteristics and to identify risk factors of schistosomiasis and STHs. Malacologic surveys were carried out at water points that are contacted by humans and animals. Principal findings: The prevalence of schistosomiasis was very low. Only two cases of S. mansoni were found (0.3%, 95% confidence interval [CI]: 0.1–1.0%). The distribution of S. haematobium was focal, with cases found only in two departments; Ferkessédougou (5.4%, 95% CI: 2.5–9.9%) and Ouangolodougou (2.7%, 95% CI: 0.9–6.3%). Hookworm was the only STH species observed with a prevalence of 1.5% (95% CI: 0.8–2.8%). A higher risk of S. haematobium infection was observed in males compared to females, but the difference was not statistically significant (2.3% versus 1.3%, odds ratio [OR]: 1.5, 95% CI: 0.8–2.7). Participants aged 16–20 years showed the highest prevalence of S. haematobium. A total of 111 human- and animal-water contact points were identified at 47 water sources. Three potential intermediate host snails of schistosomes were collected; namely, Bulinus forskalii (n = 761), Bulinus truncatus (n = 205), and Biomphalaria pfeifferi (n = 1). Yet, only one specimen of Bu. truncatus was found to be shedding schistosome cercariae. Conclusions/Significance: This study confirms very low transmission of schistosomiasis and hookworm in northern Côte d'Ivoire. The establishment and rigorous implementation of integrated surveillance-response systems could lead to the elimination of schistosomiasis and hookworm in this part of Côte d'Ivoire. Author summary: Schistosomiasis and soil-transmitted helminthiasis, the latter including, hookworms, roundworms, and whipworms, are the most widespread parasitic neglected tropical diseases. As is the case in many sub-Saharan African countries, schistosomiasis and soil-transmitted helminthiasis are endemic in Côte d'Ivoire. Mass drug administration is the mainstay of the global control strategy against schistosomiasis and soil-transmitted helminthiasis and has been implemented in Côte d'Ivoire since 2013. The new road map put forward by the World Health Organization (WHO) for the control of neglected tropical diseases aims to eliminate schistosomiasis and soil-transmitted helminthiasis as a public health problem by 2030. In light of WHO's goals, this study updates prevalence data for schistosomiasis and soil-transmitted helminthiasis and provides a deeper understanding of risk factors that drive transmission in the northern part of Côte d'Ivoire. The findings showed very low prevalence and transmission of schistosomiasis and hookworm. Participants aged 16–20 years and fishermen had the highest prevalence of urogenital schistosomiasis, with both males (2.3%) and females (1.3%) at risk of infection. The results corroborate findings from other investigations in sub-Saharan Africa, which confirm that current efforts to control schistosomiasis and soil-transmitted helminthiasis are successful. Nevertheless, further investment is still needed to reach elimination. In particular, a surveillance-response system would be a valuable tool in a low-prevalence context such as northern Côte d'Ivoire. [ABSTRACT FROM AUTHOR]

Introduction: We assessed progress in HIV viral load (VL) scale up across seven sub-Saharan African (SSA) countries and discussed challenges and strategies for improving VL coverage among patients on anti-retroviral therapy (ART). Methods: A retrospective review of VL testing was conducted in Côte d'Ivoire, Kenya, Lesotho, Malawi, Namibia, Tanzania, and Uganda from January 2016 through June 2018. Data were collected and included the cumulative number of ART patients, number of patients with ≥ 1 VL test result (within the preceding 12 months), the percent of VL test results indicating viral suppression, and the mean turnaround time for VL testing. Results: Between 2016 and 2018, the proportion of PLHIV on ART in all 7 countries increased (range 5.7%–50.2%). During the same time period, the cumulative number of patients with one or more VL test increased from 22,996 to 917,980. Overall, viral suppression rates exceeded 85% for all countries except for Côte d'Ivoire at 78% by June 2018. Reported turnaround times for VL testing results improved in 5 out of 7 countries by between 5.4 days and 27.5 days. Conclusions: These data demonstrate that remarkable progress has been made in the scale-up of HIV VL testing in the seven SSA countries. [ABSTRACT FROM AUTHOR]

In early March 2020, a few cases of COVID-19 were diagnosed in Abidjan, the capital city of Côte d'Ivoire. To combat the spread of the disease, large restrictions to mobility and gatherings were introduced between mid-March and late May 2020. We collected panel survey data on over 2,500 individuals from poorer neighborhoods of the Greater Abidjan area over the period immediately before and after the start of the pandemic. We document striking drops in employment, hours worked, income, and food consumption in the first months after the onset of COVID-19, when lockdown was in place. We also find that, in response, survey respondents received more private transfers from other parts of the country, at a time when remittances from abroad fell—and that some respondents moved either temporarily or permanently. In terms of recovery, we find that subjective well-being was lower on average in December 2020 than it was at baseline. Yet, despite schools being closed between mid-March and July 2020, school enrollment suffered little: by December 2020, enrollment rates had bounced back to their baseline level. Our results finally indicate that government policies aimed at alleviating the worst effects of lockdown only reached a few people, and not necessarily those most in need. [ABSTRACT FROM AUTHOR]

Background: This study aimed to estimate, using an HIV Recent Infection Testing Algorithm (RITA), the HIV incidence and its associated factors among female sex workers (FSW) in Côte d'Ivoire. Methods: A cross-sectional study was conducted in 2016–2017 in Abidjan and San Pedro's region among FSW aged ≥ 18 years. In addition, a sociodemographic questionnaire, HIV screening was carried out by two rapid tests. In the event of a positive result, a dried blood spot sample was taken to determine, using a RITA adapted to the Ivorian context, if it was a recent HIV infection. Results: A total of 1000 FSW were surveyed with a median age of 25 years (interquartile range: 21–29 years). 39 (3.9%) tested positive for HIV. The incidence of HIV was estimated to be 2.3 per 100 person-years, with higher incidence rates among those 24 years old or less (3.0% vs. 1.9%), non-Ivorian FSW (3.2% vs. 1.9%) and those with the lowest education level (4.6% in FSW who never went to school vs. 2.6%). The incidence seemed to be associated with the sex work practice conditions: higher incidence among FSW whose usual price was less than 3.50$ (4.3% vs.1.0%), FSW who had a larger number of clients on the last day of work (6.1% in those with 7 clients or more vs. 1.8%), FSW who reported not always using condoms with their clients (8.5% vs. 1.5%) and FSW who reported agreeing to sex without a condom in exchange for a large sum of money (10.1% vs. 1.2%). Conclusion: This study confirms that FSW remain highly exposed to HIV infection. Exposure to HIV is also clearly associated with certain sex-work factors and the material conditions of sex work. Efforts in the fight against HIV infection must be intensified to reduce new infections among FSW. [ABSTRACT FROM AUTHOR]

Background: Data on the burden and clinical epidemiology of skin wounds in rural sub-Saharan Africa is scant. The scale of the problem including preventable progression to chronic wounds, disability and systemic complications is largely unaddressed. Methods: We conducted a cross-sectional study combining active (household-based survey) and passive case finding (health services-based survey) to determine the burden and clinical epidemiology of wounds within the Taabo Health and Demographic Surveillance System (HDSS) in rural Côte d'Ivoire. Patients identified with wounds received free care and were invited to participate in the wound management study simultaneously carried out in the survey area. The data were analysed for wound prevalence, stratified by wound and patient characteristics. Results: 3842 HDSS-registered persons were surveyed. Overall wound prevalence derived from combined active and passive case finding was 13.0%. 74.1% (403/544) of patients were below the age of 15 years. Most frequent aetiologies were mechanical trauma (85.3%), furuncles (5.1%), burns (2.9%) and Buruli ulcer (2.2%). Most wounds were acute and smaller than 5 cm2 in size. 22.0% (176/799) of wounds showed evidence of secondary bacterial infection. 35.5% (22/62) of chronic wounds had persisted entirely neglected for years. Buruli ulcer prevalence was 2.3 per 1000 individuals and considerably higher than expected from an annual incidence of 0.01 per 1000 individuals as reported by WHO for Côte d'Ivoire at the time of the study. Conclusions: Skin wounds are highly prevalent in rural West Africa, where they represent a widely neglected problem. The HDSS-based survey with combined active and passive case finding adopted in this study provides a better estimate than school- and health institution-based surveys which underestimate the frequency of skin wounds and, particularly, of neglected tropical diseases of the skin, such as Buruli ulcer and yaws. A comparison with country-specific WHO data suggests underreporting of Buruli ulcer cases. Trial registration: Registration at ClinicalTrials.gov NCT03957447. Author summary: Data on the burden and clinical epidemiology of skin wounds in rural sub-Saharan Africa is scant. The scale of the problem including preventable progression to chronic wounds, disability and systemic complications is largely unaddressed. We conducted a cross-sectional study combining active (household-based survey) and passive case finding (health services-based survey) to determine the burden and clinical epidemiology of wounds within the Taabo Health and Demographic Surveillance System (HDSS) in rural Côte d'Ivoire. Patients identified were invited to participate in the wound management study simultaneously carried out in the survey area. We surveyed approximately 4000 HDSS-registered persons and found a high overall wound prevalence (13.0%), predominately in children. Mechanical trauma was the leading cause, followed by furuncles, burns and Buruli ulcer. Most wounds were acute and had a size of less than 5 cm2, but a substantial proportion was large, complicated, or chronic, some of the latter persisting neglected for years. The HDSS-based survey with combined active and passive case finding adopted in this study provides a better estimate than school- and health institution-based surveys which underestimate the frequency of skin wounds and, particularly, of neglected tropical diseases of the skin, such as Buruli ulcer and yaws. A comparison with country-specific WHO data suggests underreporting of Buruli ulcer cases. [ABSTRACT FROM AUTHOR]

Transitions between services for continued antiretroviral treatment (ART) during and after pregnancy are a commonly overlooked aspect of the HIV care cascade, but ineffective transitions can lead to poor health outcomes for women and their children. In this qualitative study, we conducted interviews with 15 key stakeholders from Ministries of Health along with PEPFAR-supported and other in-country non-governmental organizations actively engaged in national programming for adult HIV care and prevention of mother-to-child-transmission of HIV (PMTCT) services in Côte d'Ivoire, Lesotho and Malawi. We aimed to understand perspectives regarding transitions into and out of PMTCT services for continued ART. Thematic analysis revealed that, although transitions of care are necessary and a potential point of loss from ART care in all three countries, there is a lack of clear guidance on transition approach and no formal way of monitoring transition between services. Several opportunities were identified to monitor and strengthen transitions of care for continued ART along the PMTCT cascade. [ABSTRACT FROM AUTHOR]

Background: Countries are increasingly defining health benefits packages (HBPs) as a way of progressing towards Universal Health Coverage (UHC). Resources for health are commonly constrained, so it is imperative to allocate funds as efficiently as possible. We conducted allocative efficiency analyses using the Health Interventions Prioritization tool (HIPtool) to estimate the cost and impact of potential HBPs in three countries. These analyses explore the usefulness of allocative efficiency analysis and HIPtool in particular, in contributing to priority setting discussions. Methods and findings: HIPtool is an open-access and open-source allocative efficiency modelling tool. It is preloaded with publicly available data, including data on the 218 cost-effective interventions comprising the Essential UHC package identified in the 3rd Edition of Disease Control Priorities, and global burden of disease data from the Institute for Health Metrics and Evaluation. For these analyses, the data were adapted to the health systems of Armenia, Côte d'Ivoire and Zimbabwe. Local data replaced global data where possible. Optimized resource allocations were then estimated using the optimization algorithm. In Armenia, optimized spending on UHC interventions could avert 26% more disability-adjusted life years (DALYs), but even highly cost-effective interventions are not funded without an increase in the current health budget. In Côte d'Ivoire, surgical interventions, maternal and child health and health promotion interventions are scaled up under optimized spending with an estimated 22% increase in DALYs averted–mostly at the primary care level. In Zimbabwe, the estimated gain was even higher at 49% of additional DALYs averted through optimized spending. Conclusions: HIPtool applications can assist discussions around spending prioritization, HBP design and primary health care transformation. The analyses provided actionable policy recommendations regarding spending allocations across specific delivery platforms, disease programs and interventions. Resource constraints exacerbated by the COVID-19 pandemic increase the need for formal planning of resource allocation to maximize health benefits. [ABSTRACT FROM AUTHOR]

Background: Little is known about the diagnostic performance of rapid diagnostic tests (RDTs) for passive screening of human African trypanosomiasis (HAT) in Côte d'Ivoire. We determined HAT prevalence among clinical suspects, identified clinical symptoms and signs associated with HAT RDT positivity, and assessed the diagnostic tests' specificity, positive predictive value and agreement. Methods: Clinical suspects were screened with SD Bioline HAT, HAT Sero-K-Set and rHAT Sero-Strip. Seropositives were parasitologically examined, and their dried blood spots tested in trypanolysis, ELISA/Tbg, m18S-qPCR and LAMP. The HAT prevalence in the study population was calculated based on RDT positivity followed by parasitological confirmation. The association between clinical symptoms and signs and RDT positivity was determined using multivariable logistic regression. The tests' Positive Predictive Value (PPV), specificity and agreement were determined. Results: Over 29 months, 3433 clinical suspects were tested. The RDT positivity rate was 2.83%, HAT prevalence 0.06%. Individuals with sleep disturbances (p<0.001), motor disorders (p = 0.002), convulsions (p = 0.02), severe weight loss (p = 0.02) or psychiatric problems (p = 0.04) had an increased odds (odds ratios 1.7–4.6) of being HAT RDT seropositive. Specificities ranged between 97.8%-99.6% for individual RDTs, and 93.3–98.9% for subsequent tests on dried blood spots. The PPV of the individual RDTs was below 14.3% (CI 2–43), increased to 33.3% (CI 4–78) for serial RDT combinations, and reached 67% for LAMP and ELISA/Tbg on RDT positives. Agreement between diagnostic tests was poor to moderate (Kappa ≤ 0.60), except for LAMP and ELISA/Tbg (Kappa = 0.66). Conclusion: Identification of five key clinical symptoms and signs may simplify referral for HAT RDT screening. The results confirm the appropriateness of the diagnostic algorithm presently applied, with screening by SD Bioline HAT or HAT Sero-K-Set, supplemented with trypanolysis. ELISA/Tbg could replace trypanolysis and is simpler to perform. Trial registration: ClinicalTrials.gov ClinicalTrials.gov, ID NCT03356665 Author summary: As human African trypanosomiasis (HAT) or sleeping sickness is approaching elimination, case management is progressively transferred from specialized teams to front line health care centres. This approach raises practical questions. What clinical symptoms and signs should trigger HAT testing? What rapid diagnostic tests (RDT) are suitable for screening? Which unconfirmed serological suspects should be examined further? During this study conducted in Côte d'Ivoire, individuals with sleep disturbances, motor disorders, convulsions, severe weight loss, or psychiatric problems were more often positive in RDTs. These symptoms and signs should trigger referral for HAT screening. Our results confirm appropriateness of the existing HAT screening strategy with SD Bioline HAT or HAT Sero-K-Set having specificities of 97.8% and 98.9%. Subsequent tests on dried blood spots from RDT positives were 93.3% to 98.9% specific, and increased the positive predictive value from below 15% up to 67%. For selection of RDT seropositives for additional parasitological examinations, trypanolysis on dried blood spots is suitable, but could be replaced by ELISA, which can be performed locally. The optimal diagnostic test algorithm for Côte d'Ivoire, in terms of cost-effectiveness, remains to be determined. [ABSTRACT FROM AUTHOR]

Paragonimiasis is caused by zoonotic trematodes of Paragonimus spp., found in Asia, the Americas and Africa, particularly in tropical regions. These parasites have a complex, multi-host life cycle, with mammalian definitive hosts and larval stages cycling through two intermediate hosts (snails and freshwater crabs). In Africa, paragonimiasis is particularly neglected, and remains the only human parasitic disease without a fully characterised life cycle. However paragonimiasis has potentially significant impacts on public health in Africa, and prevalence has likely been underestimated through under-reporting and misdiagnosis as tuberculosis due to a similar clinical presentation. We identified the need to synthesise current knowledge and map endemic foci for African Paragonimus spp. together with Poikilorchis congolensis, a rare, taxonomically distant trematode with a similar distribution and morphology. We present the first systematic review of the literature relating to African paragonimiasis, combined with mapping of all reported occurrences of Paragonimus spp. throughout Africa, from the 1910s to the present. In human surveys, numerous reports of significant recent transmission in Southeast Nigeria were uncovered, with high prevalence and intensity of infection. Overall prevalence was significantly higher for P. uterobilateralis compared to P. africanus across studies. The potential endemicity of P. africanus in Cote d'Ivoire is also reported. In freshwater crab intermediate hosts, differences in prevalence and intensity of either P. uterobilateralis or P. africanus were evident across genus and species, suggesting differences in susceptibility. Mapping showed temporal stability of endemic foci, with the majority of known occurrences of Paragonimus found in the rainforest zone of West and Central Africa, but with several outliers elsewhere on the continent. This suggests substantial under sampling and localised infection where potential host distributions overlap. Our review highlights the urgent need for increased sampling in active disease foci in Africa, particularly using molecular analysis to fully characterise Paragonimus species and their hosts. Author summary: Paragonimiasis is a lung disease caused by food-borne zoonotic trematodes of Paragonimus spp., multi-host parasites whose complex life cycle includes primary (snail), secondary (freshwater crab), and mammalian definitive hosts. In Africa, paragonimiasis is a particularly neglected disease, where prevalence has likely been underestimated through under reporting and misdiagnosis as tuberculosis; and it remains the only human parasite without a fully known life-cycle. We present the first systematic review of paragonimiasis in Africa, including 143 publications. In human studies, we uncovered substantial recent transmission in Southeast Nigeria, and recent transmission also in Cote d'Ivoire and Cameroon in endemic foci; significantly higher prevalence of P. uterobilateralis than P. africanus; and evidence supporting the existence of P. africanus in Cote d'Ivoire. In freshwater crab intermediate hosts, prevalence and intensity of either P. uterobilateralis or P. africanus varied across genera and species, suggesting differences in susceptibility. Mapping revealed evidence of temporal stability at endemic foci in rainforest regions; and widespread outliers. Numerous reports of significant recent transmission, particularly in Southeast Nigeria should be heeded by the international NTD research community. Increased studies are urgently needed to ascertain the real distribution and diversity of Paragonimus species in Africa. [ABSTRACT FROM AUTHOR]

Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from Côte d'Ivoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa primarily due to selection imposed by other organophosphate or carbamate insecticides. Our findings highlight the predictive value of this complex resistance haplotype for phenotypic resistance and clarify its evolutionary history, providing tools to for molecular surveillance of the current and future effectiveness of pirimiphos-methyl based interventions. Author summary: Control of mosquito populations via insecticidal tools or interventions is a mainstay of campaigns to reduce malaria transmission. However, especially in sub-Saharan Africa, continued insecticidal selection pressure on the most important species of Anopheles malaria mosquitoes has favoured the evolutionary selection of increasingly effective resistance mechanisms. We investigate the genetic basis of resistance to the organophosphate pirimiphos-methyl, the dominant insecticide now used for indoor residual spraying campaigns in Africa. Genome-wide association analysis of a population from Cote d'Ivoire showed that resistant specimens share a unique combination of mutations in one gene, the acetylcholinesterase enzyme, which constitute the prime cause of pirimiphos-methyl resistance. Further testing of these mutations in diagnostic assays involving two major malaria vectors, A. coluzzii and A. gambiae, validate their use as informative predictors of pirimiphos-methyl resistance. Using data from a large collection of whole genome sequenced specimens from a broader range of locations (Burkina-Faso, Côte d'Ivoire, Ghana, and Guinea), our evolutionary analyses demonstrate that these mutations emerged in A. gambiae and transferred into A. coluzzii by inter-specific hybridisation. Our results show how resistance mechanisms in key malaria vectors have developed and spread, and provide validated tools for molecular surveillance to inform public health campaigns. [ABSTRACT FROM AUTHOR]

Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual rounds of MDA with similar compliance. The effects of MDA using ivermectin (IVM, 0.2 mg/kg) combined with albendazole (ALB, 400 mg) on the prevalence and intensity of hookworm infection were evaluated in the Abengourou (annual MDA) and Akoupé (semi-annual MDA) health Districts in eastern Côte d'Ivoire from 2014 to 2017. A cross-sectional approach was used together with mixed logistic regression, and mixed linear models. Subjects were tested for STH using the Kato-Katz technique before the first round of MDA and 12, 24, and 36 months after the first round of MDA. The mean self-reported MDA compliance assessed during the survey was 65%, and no difference was observed between treatment areas. These results were confirmed by an independent coverage survey as recommended by WHO. Hookworm was the most prevalent STH species in both areas (23.9% vs 12.4%) and the prevalence of other STH species was less than 1%. The crude prevalence of hookworm dropped significantly, from 23.9% to 5.5% (p <0.001, 77% reduction) in the annual MDA treatment area and from 12.4% to 1.9% (p <0.001, 85% reduction) in the semi-annual treatment area. The average intensity of hookworm infection decreased in the annual MDA area (406.2 epg to 118.3 epg), but not in the semi-annual MDA area (804.9 epg to 875.0 epg). Moderate and heavy infections (1% and 1.3% at baseline) were reduced to 0% and 0.4% in the annual and semi-annual treatment areas, respectively. Using a mixed logistic regression model, and after adjusting for baseline prevalence, only the year 2 re-examination showed a difference in prevalence between treatments (OR: 2.26 [95% CI: 1.03, 4.98], p = 0.043). Analysis of intensity of hookworm infection indicated also that treatment differences varied by follow-up visit. In conclusion twelve months after the last treatment cycle, three annual and five semi-annual rounds of community-wide MDA with the combination of IVM and ALB showed strong, but similar impact on hookworm prevalence and intensity in eastern Côte d'Ivoire. Therefore, an annual MDA regimen seems to be an efficient strategy to control hookworm infection in endemic areas with low and moderate infection prevalence. Trial registration: The study was registered at ClinicalTrial.gov under the number NTC02032043. Author summary: Community-wide MDA to eliminate LF and onchocerciasis has the beneficial effect to reduce also STH infections. The objective of the current study was to determine whether five semi-annual rounds of MDA have a greater impact on STH than three annual rounds of MDA using ivermectin combined with albendazole. In Abengourou and Akoupé health Districts in eastern Côte d'Ivoire the prevalence and intensity of hookworm infection were evaluated before and after MDA. Prior to MDA and after each annual treatment cycle, study participants were tested for STH using the Kato-Katz technique. The mean MDA compliance assessed during the survey was 65%, and no difference was observed between treatment areas. Compliance results were confirmed by an independent coverage survey as recommended by WHO. Hookworm was the most prevalent STH species in both areas and the prevalence of other STH species was less than 1%. The crude prevalence of hookworm dropped significantly, from 23.9% to 5.5% in the annual and from 12.4% to 1.9% in the semi-annual treatment areas. The intensity of hookworm infection in infected persons decreased significantly in the annual MDA area (406.2 epg to 118.3 epg, p = 0.017), but not in the semi-annual MDA area (804.9 epg to 875.0 epg, p = 0.216). Moderate and heavy infections were reduced to less than 1% in both treatment areas. Three annual and five semi-annual rounds of community-wide MDA with the combination of IVM and ALB showed strong, but similar effects on hookworm prevalence and intensity in eastern Côte d'Ivoire. Therefore, an annual MDA regimen seems to be an efficient strategy for controlling hookworm infection in endemic areas with low and moderate infection prevalence. [ABSTRACT FROM AUTHOR]

Monitoring of cyanobacteria in freshwater ecosystems is a complex task, which is time consuming and expensive due to the chaotic population dynamics and highly heterogeneous distribution of cyanobacteria populations in water bodies. The financial cost constitutes a strong limitation for the implementation of long-term monitoring programs in developing countries, particularly in Africa. The work presented here was performed in the framework of an international project addressing the sustainable monitoring and management of surface water resources used for the production of drinking water in three African countries. We tested the potential of a citizen approach for monitoring cyanobacterial blooms, which are a growing threat to the drinking water supply. This pilot study was designed, implemented and evaluated in close interaction with the Pasteur Institute of the Ivory Coast and with the populations of three villages located on the shoreline of a freshwater lagoon located near Abidjan city. Based on the use of a smartphone application, the citizens of the three villages were invited to report water color changes, as these changes could reflect cyanobacteria proliferations. A two-year experimentation period has shown that it is possible to mobilize the local populations to monitor cyanobacterial blooms. The data collected by citizens were consistent with the data obtained by a classical monitoring of cyanobacteria performed over seven months, but it appeared that new approaches were needed to validate the citizen data. This participatory approach also provided great improvements to the understanding and awareness of local populations regarding water quality and cyanobacterial bloom issues. Finally, we discuss some of the difficulties and limitations of our participatory monitoring approach that should be considered by further implementations. Despite these difficulties, our work suggests that citizen monitoring is a promising approach that may complement the classical approach to sustainable monitoring of cyanobacteria in developing countries. [ABSTRACT FROM AUTHOR]

Background: Significant efforts to control human African trypanosomiasis (HAT) over the two past decades have resulted in drastic decrease of its prevalence in Côte d'Ivoire. In this context, passive surveillance, integrated in the national health system and based on clinical suspicion, was reinforced. We describe here the health-seeking pathway of a girl who was the first HAT patient diagnosed through this strategy in August 2017. Methods: After definitive diagnosis of this patient, epidemiological investigations were carried out into the clinical evolution and the health and therapeutic itinerary of the patient before diagnosis. Results: At the time of diagnosis, the patient was positive in both serological and molecular tests and trypanosomes were detected in blood and cerebrospinal fluid. She suffered from important neurological disorders. The first disease symptoms had appeared three years earlier, and the patient had visited several public and private peripheral health care centres and hospitals in different cities. The failure to diagnose HAT for such a long time caused significant health deterioration and was an important financial burden for the family. Conclusion: This description illustrates the complexity of detecting the last HAT cases due to complex diagnosis and the progressive disinterest and unawareness by both health professionals and the population. It confirms the need of implementing passive surveillance in combination with continued sensitization and health staff training. Author summary: Human African trypanosomiasis (HAT) or sleeping sickness is a parasitic disease caused by Trypanosoma brucei that is transmitted by tsetse flies. In 2012, HAT was included in the World Health Organization roadmap for the control of neglected tropical diseases with the objective of elimination as a public health problem by 2020. In Côte d'Ivoire, HAT prevalence has dropped sharply the last decade. A passive HAT surveillance was therefore integrated in the national health system, which allowed to detect a first patient in 2017. This article describes the complex health seeking pathway and suffering before diagnosis of this patient, an 11 years old girl, and illustrates the challenge when health agents and population no longer consider HAT as a threat in an elimination context. Our results show the need to install a solid surveillance system, in combination with continued sensitization and repeated health staff training. [ABSTRACT FROM AUTHOR]

Background: Whereas 72% of hepatitis C virus (HCV)-infected people worldwide live in low- and middle-income countries (LMICs), only 6% of them have been diagnosed. Innovative technologies for HCV diagnosis provide opportunities for developing testing strategies more adapted to resource-constrained settings. However, studies about their economic feasibility in LMICs are lacking. Methods: Adopting a health sector perspective in Cameroon, Cote-d'Ivoire, and Senegal, a decision tree model was developed to compare 12 testing strategies with the following characteristics: a one-step or two-step testing sequence, HCV-RNA or HCV core antigen as confirmative biomarker, laboratory or point-of-care (POC) tests, and venous blood samples or dried blood spots (DBS). Outcomes measures were the number of true positives (TPs), cost per screened individual, incremental cost-effectiveness ratios, and nationwide budget. Corresponding time horizon was immediate, and outcomes were accordingly not discounted. Detailed sensitivity analyses were conducted. Findings: In the base-case, a two-step POC-based strategy including anti-HCV antibody (HCV-Ab) and HCV-RNA testing had the lowest cost, €8.18 per screened individual. Assuming a lost-to-follow-up rate after screening > 1.9%, a DBS-based laboratory HCV-RNA after HCV-Ab POC testing was the single un-dominated strategy, requiring an additional cost of €3653.56 per additional TP detected. Both strategies would require 8–25% of the annual public health expenditure of the study countries for diagnosing 30% of HCV-infected individuals. Assuming a seroprevalence > 46.9% or a cost of POC HCV-RNA < €7.32, a one-step strategy based on POC HCV-RNA dominated the two-step POC-based strategy but resulted in many more false-positive cases. Conclusions: POC HCV-Ab followed by either POC- or DBS-based HCV-RNA testing would be the most cost-effective strategies in the study countries. Without a substantial increase in funding for health or a dramatic decrease in assay prices, HCV testing would constitute an economic barrier to the implementation of HCV elimination programs in LMICs. [ABSTRACT FROM AUTHOR]

Background: Density dependence in helminth establishment and heterogeneity in exposure to infection are known to drive resilience to interventions based on mass drug administration (MDA). However, the interaction between these processes is poorly understood. We developed a novel individual-based model for onchocerciasis transmission, EPIONCHO-IBM, which accounts for both processes. We fit the model to pre-intervention epidemiological data and explore parasite dynamics during MDA with ivermectin. Methodology/Principal findings: Density dependence and heterogeneity in exposure to blackfly (vector) bites were estimated by fitting the model to matched pre-intervention microfilarial prevalence, microfilarial intensity and vector biting rate data from savannah areas of Cameroon and Côte d'Ivoire/Burkina Faso using Latin hypercube sampling. Transmission dynamics during 25 years of annual and biannual ivermectin MDA were investigated. Density dependence in parasite establishment within humans was estimated for different levels of (fixed) exposure heterogeneity to understand how parametric uncertainty may influence treatment dynamics. Stronger overdispersion in exposure to blackfly bites results in the estimation of stronger density-dependent parasite establishment within humans, consequently increasing resilience to MDA. For all levels of exposure heterogeneity tested, the model predicts a departure from the functional forms for density dependence assumed in the deterministic version of the model. Conclusions/Significance: This is the first, stochastic model of onchocerciasis, that accounts for and estimates density-dependent parasite establishment in humans alongside exposure heterogeneity. Capturing the interaction between these processes is fundamental to our understanding of resilience to MDA interventions. Given that uncertainty in these processes results in very different treatment dynamics, collecting data on exposure heterogeneity would be essential for improving model predictions during MDA. We discuss possible ways in which such data may be collected as well as the importance of better understanding the effects of immunological responses on establishing parasites prior to and during ivermectin treatment. Author summary: Onchocerciasis, caused by the helminth parasite Onchocerca volvulus, is transmitted via the bites of Simulium blackflies. The World Health Organization has proposed onchocerciasis elimination in African countries by 2020/2025. Processes regulating parasite abundance in the lifecycle of helminths are known to influence the endemic prevalence in mathematical models. For example, when transmission intensity is low, a high proportion of incoming parasites may establish within a human host, whilst the opposite may be true when transmission intensity is high, possibly due to immunological processes. These processes may interact with exposure as some people are bitten more than others and receive more parasites. Therefore, regulatory processes that depend on parasite density and inter-individual variation in exposure play a central role in the ability of transmission to bounce back following mass drug administration. The former, because they may increase the success of parasite establishment as treatment progresses; the latter, because a few highly infected individuals may maintain transmission. We developed an individual-based model for onchocerciasis transmission and show that the interaction between these two processes impacts treatment outcomes. We highlight the need to obtain data on exposure to vector bites and to understand how immunological processes potentially regulating parasite establishment change under treatment. [ABSTRACT FROM AUTHOR]

Background: In Côte d’Ivoire, people living with HIV (PLHIV) have free access to antiretroviral therapy (ART) and cotrimoxazole. Yet, they may use other medications to treat non-HIV diseases. Scarce data are available regarding the use of non-HIV medications in Africa. This study describes the use of non-HIV medications and identifies the factors associated with their use by PLHIV on ART in Côte d’Ivoire. Methods: A cross-sectional study was conducted in six HIV clinics in 2016. HIV-1-infected adults receiving ART for at least one year were eligible. A standardized questionnaire was used to collect demographics, HIV characteristics and medication use data. Associated factors were identified using a multivariate adjusted Poisson regression. Results: A total of 1,458 participants (74% women) were enrolled. The median age was 44 years, and the median duration of ART was 81 months. A total of 696 (48%) participants reported having used at least one non-HIV medication. Among the 1,519 non-HIV medications used, 550 (36%) had not been prescribed and 397 (26%) were from the nervous system class. Individuals who were more likely to report the use of at least one non-HIV medication included those who had been treated in an Abidjan HIV clinic, had a high school education level, had a monthly income between 152 and 304 euros, had a poor perceived health status, had WHO advanced clinical stage, had used traditional medicine products and had not used cotrimoxazole. Conclusion: Almost half PLHIV on ART reported using non-HIV medication. Further research is needed to assess whether the use of non-HIV medication is appropriate given about a third of those medications are not being prescribed. [ABSTRACT FROM AUTHOR]

Background: There is evidence from experimental hut and household studies that the entomological efficacy of long lasting pyrethroid treated nets (LLINs) is compromised in areas of pyrethroid resistance. The rapid increase in resistance intensity in African malaria vectors could further undermine the performance of these nets. The pyrethroid resistance intensity in Anopheles gambiae s.l. M’bé from central Côte d’Ivoire is reported to be high (> 1700 fold). Whether this translates into an increase in entomological indicators of malaria transmission needs investigation. Method: The efficacy of two long lasting insecticidal nets (LN) MiraNet and MagNet, both alpha-cypermethrin based was evaluated in experimental huts against pyrethroid resistant Anopheles gambiae in M’bé, central Côte d’Ivoire. All nets were deliberately holed to simulate wear-and-tear and were tested unwashed and after 20 standardized washes. Results: The entry rates of An. gambiae s.l. into huts with insecticide treated nets were 62–84% lower than entry into huts with untreated nets (p < 0.001). Exit rates of An. gambiae s.l. with unwashed MiraNet and MagNet LNs were significantly greater than with untreated nets (50–60% vs 26%) and this effect after washing 20 times nets did not decrease. Blood-feeding with both nets was significantly inhibited relative to the untreated reference net (31–55%) (p < 0.001). Washing MiraNet LN 20 times had no significant impact on protection against An. gambiae s.l. bites but it did cause a significant fall by 40% in protection with MagNet LN (p < 0.001). All insecticide treated nets induced higher mortality of An. gambiae s.l. than the untreated net (p < 0.05). The impact though significant was limited (14–30%). The personal protection against An. gambiae s.l. bites derived from all treatments was high (75–90%). The overall insecticidal effect was compromised by pyrethroid resistance and was not detectable in some treatments. Conclusion: In this area of high pyrethroid resistance intensity (over 1700 fold), both MiraNet and MagNet LNs still conferred appreciable personal protection against mosquito bites despite inducing only slightly greater mortality of pyrethroid resistant Anopheles mosquitoes than untreated nets. The impact is comparable to moderately intense Benin resistance area (207 fold) and Burkina Faso (over 1000 fold). This preserved level of protection plus the small but sensitive killing of mosquitoes may continue to impact vectorial capacity despite high intensity of resistance. Nevertheless, there is an obvious need for strategies and nets with novel mode of action to enhance vector control. [ABSTRACT FROM AUTHOR]

Background: In Côte d’Ivoire, tuberculosis (TB) is a common cause of death among HIV-infected antiretroviral therapy (ART) enrollees. Ivorian guidelines recommend screening for TB and initiation of TB treatment before ART initiation. Compliance with these guidelines can help reduce TB-related mortality during ART and possibly nosocomial TB transmission. Methods and Findings: In a retrospective cohort study among 3,682 randomly selected adults (≥15 years old) starting ART during 2004–2007 at 34 randomly selected facilities, documentation of TB screening completion, prevalence of active TB at ART initiation, and incidence of TB during ART were evaluated. At ART initiation, median age was 36 years, 67% were female, and median CD4 count was 135 cells/μL. Among all 3,682 enrollees, 73 (2%) were on TB treatment at the time of referral to the ART facility. Among the 3,609 not on TB treatment, 1,263 (36%) were documented to receive some TB screening before ART initiation; 21% were screened for cough, 21% for weight loss, 18% for fever, 18% for TB contacts, and 12% for night sweats. Among the 1,263 screened, 111 (11%) were diagnosed with TB and started TB treatment before ART. No associations between patient characteristics and probability of being screened were noted. However, documentation of TB screening completion before ART varied widely by ART facility from 0–100%. TB incidence during ART was 3.0 per 100 person-years but varied widely by ART facility from 0/100 person-year to 13.1/100 person-years. Conclusions: Screening for TB before ART initiation was poorly documented. Facility-level variations in TB screening documentation suggest facility-level factors, such as investment in training programs, might determine documentation practices. Targeting under-performing ART facilities with improvement activities is needed. Variations among facilities in TB incidence warrant further research. These incidence variations could reflect differences between facilities in TB screening, diagnostic tests, documentation practices, or TB risk possibly related to infection control practices or local community TB incidence. [ABSTRACT FROM AUTHOR]

Background: Ivory Coast is a West African country with the highest reported cases of Buruli ulcer, a disabling subcutaneous infection due to Mycobacterium ulcerans. However, the prevalence of environmental M. ulcerans is poorly known in this country. Methods: We collected 496 environmental specimens consisting of soil (n = 100), stagnant water (n = 200), plants (n = 100) and animal feces (n = 96) in Ivory Coast over five months in the dry and wet seasons in regions which are free of Buruli ulcer (control group A; 250 specimens) and in regions where the Buruli ulcer is endemic (group B; 246 specimens). After appropriate total DNA extraction incorporating an internal control, the M. ulcerans IS2404 and KR-B gene were amplified by real-time PCR in samples. In parallel, a calibration curve was done for M. ulcerans Agy99 IS2404 and KR-B gene. Results: Of 460 samples free of PCR inhibition, a positive real-time PCR detection of insertion sequence IS2404 and KR-B gene was observed in 1/230 specimens in control group A versus 9/230 specimens in group B (P = 0.02; Fisher exact test). Positive specimens comprised seven stagnant water specimens, two feces specimens confirmed to be of Thryonomys swinderianus (agouti) origin by real-time PCR of the cytb gene; and one soil specimen. Extrapolation from the calibration curves indicated low inoculums ranging from 1 to 102 mycobacteria/mL. Conclusion: This study confirms the presence of M. ulcerans in the watery environment surrounding patients with Buruli ulcer in Ivory Coast. It suggests that the agouti, which is in close contacts with populations, could play a role in the environmental cycle of M. ulcerans, as previously suggested for the closely related possums in Australia. [ABSTRACT FROM AUTHOR]

Background: HIV infection increases a woman’s risk for cervical cancer, and cervical cancer incidence and mortality rates are higher in countries with high HIV prevalence and limited resources for screening. Visual inspection with acetic acid (VIA) allows screening and treatment of cervical lesions in a single-visit approach (SVA), but data on its performance in HIV-infected women are limited. This study’s objective was to examine cervical cancer screening using VIA/SVA in programs serving HIV-infected women. Methods: A VIA/SVA program with cryotherapy for VIA-positive lesions was implemented in Côte d’Ivoire, Guyana, and Tanzania from 2009 to 2012. The effect of HIV status on VIA positivity and on presence of cryotherapy-eligible lesions was examined using a cross-sectional study design, with Chi-square tests for comparisons and constructed multivariate logistic regression models. A P-value of < 0.05 was significant. Findings: VIA was performed on 34,921 women, 10% (3,580) were VIA positive; 2,508 (85%) eligible women received cryotherapy during the same visit; only 234 (52%) of those who postponed returned for treatment; 622 (17%) VIA-positive women had lesions too large to be treated with cryotherapy and were referred for excisional treatment. In multivariate analysis—controlling for HIV status, location of the screening clinic, facility location, facility type, and country—compared to HIV-uninfected/unknown women, HIV-infected women had higher odds of being VIA positive (OR 1.95, 95% CI 1.76, 2.16, P<0.0001) and of having large lesions requiring referral (OR 1.93, 95% CI 1.49, 2.51, P< 0.0001). Minor treatment complications occurred in 19 of 3,032 (0.63%) women; none required further intervention. Conclusions: This study found that compared to HIV-uninfected/unknown women, HIV-infected women had nearly twice the odds of being VIA-positive and to require referral for large lesions. SVA was safe and resulted in significant reductions in loss to follow-up. There is increased need for excisional treatment in countries with high HIV prevalence. [ABSTRACT FROM AUTHOR]

Background: Individual rapid tests for serodiagnosis (RDT) of human African trypanosomiasis (HAT) are particularly suited for passive screening and surveillance. However, so far, no large scale evaluation of RDTs has been performed for diagnosis of Trypanosoma brucei gambiense HAT in West Africa. The objective of this study was to assess the diagnostic accuracy of 2 commercial HAT-RDTs on stored plasma samples from West Africa. Methodology/Principal findings: SD Bioline HAT and HAT Sero-K-Set were performed on 722 plasma samples originating from Guinea and Côte d'Ivoire, including 231 parasitologically confirmed HAT patients, 257 healthy controls, and 234 unconfirmed individuals whose blood tested antibody positive in the card agglutination test but negative by parasitological tests. Immune trypanolysis was performed as a reference test for trypanosome specific antibody presence. Sensitivities in HAT patients were respectively 99.6% for SD Bioline HAT, and 99.1% for HAT Sero-K-Set, specificities in healthy controls were respectively 87.9% and 88.3%. Considering combined positivity in both RDTs, increased the specificity significantly (p≤0.0003) to 93.4%, while 98.7% sensitivity was maintained. Specificities in controls were 98.7–99.6% for the combination of one or two RDTs with trypanolysis, maintaining a sensitivity of at least 98.1%. Conclusions/Significance: The observed specificity of the single RDTs was relatively low. Serial application of SD Bioline HAT and HAT Sero-K-Set might offer superior specificity compared to a single RDT, maintaining high sensitivity. The combination of one or two RDTs with trypanolysis seems promising for HAT surveillance. Author Summary: Screening for gambiense human African trypanosomiasis (HAT) or sleeping sickness is traditionally based on detection of trypanosome specific antibodies in blood. Whereas the card agglutination test is particularly suited for mass screening, individual rapid serodiagnostic tests (RDTs) are rather adapted for use in peripheral health-care centres. Two RDTs have been commercialized recently, and we assessed their diagnostic accuracy on stored plasma samples from West Africa. Immune trypanolysis was performed as a laboratory reference test for antibody presence. Although sensitivity for serodiagnosis of HAT in West Africa was high for both RDTs, their specificity was only 88%. Taking into account the high number of false positive test results, combined seropositivity in both RDTs was considered, raising specificity to 93%. Serial application of two RDTs should therefore be considered as an option for passive case finding, especially in settings with low HAT prevalence. A combination of one or two RDTs with immune trypanolysis further improved specificity for HAT to 99%, while maintaining sensitivity at 99% and seems promising for HAT surveillance. [ABSTRACT FROM AUTHOR]

Background: Schistosoma haematobium and Schistosoma mansoni are blood flukes that cause urogenital and intestinal schistosomiasis, respectively. In Côte d′Ivoire, both species are endemic and control efforts are being scaled up. Accurate knowledge of the geographical distribution, including delineation of high-risk areas, is a central feature for spatial targeting of interventions. Thus far, model-based predictive risk mapping of schistosomiasis has relied on historical data of separate parasite species. Methodology: We analyzed data pertaining to Schistosoma infection among school-aged children obtained from a national, cross-sectional survey conducted between November 2011 and February 2012. More than 5,000 children in 92 schools across Côte d′Ivoire participated. Bayesian geostatistical multinomial models were developed to assess infection risk, including S. haematobium–S. mansoni co-infection. The predicted risk of schistosomiasis was utilized to estimate the number of children that need preventive chemotherapy with praziquantel according to World Health Organization guidelines. Principal Findings: We estimated that 8.9% of school-aged children in Côte d′Ivoire are affected by schistosomiasis; 5.3% with S. haematobium and 3.8% with S. mansoni. Approximately 2 million annualized praziquantel treatments would be required for preventive chemotherapy at health districts level. The distinct spatial patterns of S. haematobium and S. mansoni imply that co-infection is of little importance across the country. Conclusions/Significance: We provide a comprehensive analysis of the spatial distribution of schistosomiasis risk among school-aged children in Côte d′Ivoire and a strong empirical basis for a rational targeting of control interventions. Author Summary: Two types of blood-dwelling parasitic worms that cause schistosomiasis (i.e., Schistosoma haematobium and Schistosoma mansoni) are endemic in Côte d′Ivoire, West Africa. Reliable information on their geographical distribution is needed to plan and guide the national control program. Recently, control efforts have been intensified. There is a need to update risk maps that, historically, have been based on data specific to each type of parasite. In late 2011 and early 2012, we conducted a cross-sectional survey in 92 schools all over Côte d′Ivoire. We used Bayesian geostatistical multinomial models to estimate the risk for each infection, as well as co-infection. We estimated that slightly less than 10% of school-aged children are affected by schistosomiasis (5.3% with S. haematobium and 3.8% with S. mansoni). To control schistosomiasis with the deworming drug praziquantel, approximately 2 million treatments would be necessary each year. The distinct spatial patterns of S. haematobium and S. mansoni imply that co-infection with these two types of parasitic worms is rare across the country. Our results provide a detailed analysis of the spatial distribution of schistosomiasis risk among school-aged children in Côte d′Ivoire, which will inform the national control program for targeted interventions. [ABSTRACT FROM AUTHOR]

Background: Parasitic infections are still of considerable public health relevance, notably among children in low- and middle-income countries. Measures to assess the magnitude of ill-health in infected individuals, however, are debated and patient-based proxies through generic health-related quality of life (HrQoL) instruments are among the proposed strategies. Disability estimates based on HrQoL are still scarce and conflicting, and hence, there is a need to strengthen the current evidence-base. Methodology: Between November 2011 and February 2012, a national school-based cross-sectional survey was conducted in Côte d'Ivoire. Children underwent parasitological and clinical examination to assess infection status with Plasmodium and helminth species and clinical parameters, and responded to a questionnaire interview incorporating sociodemographic characteristics, self-reported morbidity, and HrQoL. Validity analysis of the HrQoL instrument was performed, assessing floor and ceiling effects, internal consistency, and correlation with morbidity scores. Multivariate regression models were applied to identify significant associations between HrQoL and children's parasitic infection and clinical status. Principal Findings: Parasitological examination of 4,848 children aged 5–16 years revealed Plasmodium spp., hookworm, Schistosoma haematobium, Schistosoma mansoni, Ascaris lumbricoides, and Trichuris trichiura prevalences of 75.0%, 17.2%, 5.7%, 3.7%, 1.8%, and 1.3%, respectively. Anemic children showed a significant 1-point reduction in self-rated HrQoL on a scale from 0 to 100, whereas no significant negative association between HrQoL and parasite infection was observed. The 12-item HrQoL questionnaire proofed useful, as floor and ceiling effects were negligible, internally consistent (Cronbach's alpha = 0.71), and valid, as revealed by significant negative correlations and associations with children's self-reported and clinically assessed morbidity. Conclusions/Significance: Our results suggest that HrQoL tools are not sufficiently sensitive to assess subtle morbidities due to parasitic infection in Ivorian school-aged children. However, more advanced morbid sequelae (e.g., anemia), were measurable by the instrument's health construct. Further investigations on health impacts of parasitic infection among school-aged children and refinement of generic HrQoL questionnaires are warranted. Author Summary: Infectious diseases like malaria and parasitic worms affect hundreds of millions of people, and impact physical and cognitive development of children in Africa, Asia, and the Americas. Over the past 20 years, it was debated how the magnitude of ill-health due to these conditions should be assessed. One proposed strategy was to include patient-based ratings of wellbeing by administration of health-related quality of life (HrQoL) questionnaires. In order to provide new evidence on disability from parasitic infections, we conducted HrQoL interviews with children aged 5–16 years from 92 schools across Côte d'Ivoire. Children were examined for parasitic infections and clinical signs like anemia, malnutrition, and organ enlargement. We compared the self-rated HrQoL of infected and non-infected children and also considered their sociodemographic background. We could not identify lowered HrQoL in infected children, but we found that children with anemia reported a 1-point lower score on a 100-point HrQoL scale in comparison with their non-anemic counterparts. We consider our HrQoL questionnaire as useful and valid, but would recommend its further testing and development in few purposefully selected settings. Further investigation of disability induced by malaria and parasitic worm infections is warranted. [ABSTRACT FROM AUTHOR]

Background: Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against schistosomiasis. The antimalarial drug mefloquine shows antischistosomal activity in animal models and clinical trials, which calls for further investigations. Methodology: We comparatively assessed the efficacy and tolerability of the following treatments against Schistosoma haematobium in school-aged children in Côte d'Ivoire: (i) praziquantel (40 mg/kg; standard treatment); (ii) mefloquine (25 mg/kg) combined with praziquantel (40 mg/kg); and (iii) mefloquine-artesunate (3× (100 mg artesunate +250 mg mefloquine)) combined with praziquantel (40 mg/kg) (treatments administered on subsequent days). Two urine samples were collected before, and on days 21–22 and 78–79 after the first dosing. Principal Findings: Sixty-one children were present on all examination time points and had complete datasets. No difference in efficacy was observed between the three treatment groups on either follow-up. On the 21–22 day posttreatment follow-up, based on available case analysis, cure rates of 33% (95% confidence interval (CI) 11–55%), 29% (95% CI 8–50%), and 26% (95% CI 5–48%) were observed for praziquantel, mefloquine-artesunate-praziquantel, and mefloquine-praziquantel, respectively. The corresponding egg reduction rates were 94% and above. On the second follow-up, observed cure rates ranged from 19% (praziquantel) to 33% (mefloquine-artesunate-praziquantel), and egg reduction rates were above 90%. Praziquantel monotherapy was the best tolerated treatment. In the mefloquine-artesunate-praziquantel group, adverse events were reported by 91% of the participants, and in the mefloquine-praziquantel group, 95% experienced adverse events. With the exception of abdominal pain at moderate severity, adverse events were mild. Conclusions/Significance: The addition of mefloquine or mefloquine-artesunate does not increase the efficacy of praziquantel against chronic S. haematobium infection. Additional studies are necessary to elucidate the effect of the combinations against acute schistosomiasis. Author Summary: The antimalarial drug mefloquine shows activity against blood flukes that cause the disease schistosomiasis. In animal studies it has been found that a mefloquine-praziquantel combination kills blood flukes more effectively than praziquantel alone. Combining praziquantel with another drug might therefore increase efficacy, broaden the spectrum of activity, and delay the development of drug resistance. We designed a study in Ivorian school children to assess the efficacy and tolerability of mefloquine and mefloquine-artesunate combined with praziquantel against the blood fluke Schistosoma haematobium. The administration of the antimalarials and praziquantel was spaced by a day. Treatment outcomes were assessed twice, on days 21–22 and 78–79 after the first dosing to determine the effect against adult and juvenile S. haematobium, respectively. At both follow-ups, high reduction in the intensity of infection (egg reduction rates of 94–96%), but low cure rates (26–33%) were observed in the three treatment groups. Adverse events were common, particularly in children treated with mefloquine-praziquantel and mefloquine-artesunate-praziquantel. Our study suggests that the addition of mefloquine and mefloquine-artesunate to praziquantel has no benefit in the treatment of chronic S. haematobium infection. However, further investigations are warranted to evaluate the effect of combination therapy on juvenile flukes and longer-term morbidity profiles. [ABSTRACT FROM AUTHOR]

Background: Helminth infection and malaria remain major causes of ill-health in the tropics and subtropics. There are several shared risk factors (e.g., poverty), and hence, helminth infection and malaria overlap geographically and temporally. However, the extent and consequences of helminth-Plasmodium co-infection at different spatial scales are poorly understood. Methodology: This study was conducted in 92 schools across Côte d'Ivoire during the dry season, from November 2011 to February 2012. School children provided blood samples for detection of Plasmodium infection, stool samples for diagnosis of soil-transmitted helminth (STH) and Schistosoma mansoni infections, and urine samples for appraisal of Schistosoma haematobium infection. A questionnaire was administered to obtain demographic, socioeconomic, and behavioral data. Multinomial regression models were utilized to determine risk factors for STH-Plasmodium and Schistosoma-Plasmodium co-infection. Principal Findings: Complete parasitological and questionnaire data were available for 5,104 children aged 5-16 years. 26.2% of the children were infected with any helminth species, whilst the prevalence of Plasmodium infection was 63.3%. STH-Plasmodium co-infection was detected in 13.5% and Schistosoma-Plasmodium in 5.6% of the children. Multinomial regression analysis revealed that boys, children aged 10 years and above, and activities involving close contact to water were significantly and positively associated with STH-Plasmodium co-infection. Boys, wells as source of drinking water, and water contact were significantly and positively associated with Schistosoma-Plasmodium co-infection. Access to latrines, deworming, higher socioeconomic status, and living in urban settings were negatively associated with STH-Plasmodium co-infection; whilst use of deworming drugs and access to modern latrines were negatively associated with Schistosoma-Plasmodium co-infection. Conclusions/Significance: More than 60% of the school children surveyed were infected with Plasmodium across Côte d'Ivoire, and about one out of six had a helminth-Plasmodium co-infection. Our findings provide a rationale to combine control interventions that simultaneously aim at helminthiases and malaria. Author Summary: Parasitic worm infection and malaria are common in tropical and subtropical countries and many people suffer from multiple parasite infections concurrently. It is important to gain knowledge on co-endemicity patterns because such information can help to design and prioritize interventions and control strategies focusing on areas at highest risk of co-infection. We carried out the first national survey on parasitic worm and Plasmodium infection among children in 92 schools all over Côte d'Ivoire. Questionnaires were administered to determine the children's socioeconomic status and infection-related risk factors. We found an overall prevalence of Plasmodium infection of 63.3%. Hookworm was the most common parasitic worm infection (17.2%), whereas schistosome worms were more focally distributed (9.1%). One out of six children was co-infected with parasitic worms and Plasmodium. Children from the poorest households living in rural areas were at highest risk of co-infection. The lack of sanitation facilities, and activities like swimming or fishing in nearby rivers were found to be positively associated with multiple species parasite infection. Our study motivates the integration of combined intervention measures that concurrently target neglected tropical diseases and malaria in highly resource-constrained settings. [ABSTRACT FROM AUTHOR]

Background: Facing the dual burden of invasive cervical cancer and HIV in sub-Saharan Africa, the identification of preventable determinants of Cervical Intraepithelial Neoplasia (CIN) in HIV-infected women is of paramount importance. Methods: A cervical cancer screening based on visual inspection methods was proposed to HIV-infected women in care in Abidjan, Côte d'Ivoire. Positively screened women were referred for a colposcopy to a gynaecologist who performed directed biopsies. Results: Of the 2,998 HIV-infected women enrolled, 132 (4.4%) CIN of any grade (CIN+) were identified. Women had been followed-up for a median duration of three years [IQR: 1–5] and 76% were on antiretroviral treatment (ART). Their median most recent CD4 count was 452 [IQR: 301–621] cells/mm3. In multivariate analysis, CIN+ was associated with a most recent CD4 count >350 cells/mm3 (OR: 0.3; 95% CI: 0.2–0.6) or ≥200–350 cells/mm3 (OR 0.6; 95% CI 0.4–1.0) (Ref: <200 cells/mm3 CD4) (p<10−4). Conclusions: The presence of CIN+ is less common among HIV-infected women with limited or no immune deficiency. Despite the potential impact of immunological recovery on the reduction of premalignant cervical lesions through the use of ART, cervical cancer prevention, including screening and vaccination remains a priority in West Africa while ART is rolled-out. [ABSTRACT FROM AUTHOR]

Background: The Kato-Katz technique is widely used for the diagnosis of Schistosoma mansoni, but shows low sensitivity in light-intensity infections. We assessed the accuracy of a commercially available point-of-care circulating cathodic antigen (POC-CCA) cassette test for the diagnosis of S. mansoni in preschool-aged children before and after praziquantel administration. Methodology: A 3-week longitudinal survey with a treatment intervention was conducted in Azaguié, south Côte d'Ivoire. Overall, 242 preschoolers (age range: 2 months to 5.5 years) submitted two stool and two urine samples before praziquantel administration, and 86 individuals were followed-up posttreatment. Stool samples were examined with duplicate Kato-Katz thick smears for S. mansoni. Urine samples were subjected to POC-CCA cassette test for S. mansoni, and a filtration method for S. haematobium diagnosis. Principal Findings: Before treatment, the prevalence of S. mansoni, as determined by quadruplicate Kato-Katz, single CCA considering 'trace' as negative (t−), and single CCA with 'trace' as positive (t+), was 23.1%, 34.3% and 64.5%, respectively. Using the combined results (i.e., four Kato-Katz and duplicate CCA(t−)) as diagnostic 'gold' standard, the sensitivity of a single Kato-Katz, a single CCA(t−) or CCA(t+) was 28.3%, 69.7% and 89.1%, respectively. Three weeks posttreatment, the sensitivity of a single Kato-Katz, single CCA(t−) and CCA(t+) was 4.0%, 80.0% and 84.0%, respectively. The intensity of the POC-CCA test band reaction was correlated with S. mansoni egg burden (odds ratio = 1.2, p = 0.04). Conclusions/Significance: A single POC-CCA cassette test appears to be more sensitive than multiple Kato-Katz thick smears for the diagnosis of S. mansoni in preschool-aged children before and after praziquantel administration. The POC-CCA cassette test can be recommended for the rapid identification of S. mansoni infections before treatment. Additional studies are warranted to determine the usefulness of POC-CCA for assessing drug efficacy and monitoring the impact of control interventions. Author Summary: The strategy to control morbidity due to infection with the blood fluke Schistosoma mansoni is to regularly treat school-aged children with the drug praziquantel. Recent studies suggest that in highly endemic areas preschoolers might need to be included in such deworming campaigns. An accurate diagnosis is important to assess how many preschool-aged children need treatment, but the widely used Kato-Katz technique does not detect all infections. We assessed the accuracy of a point-of-care (POC) test that is based on the detection of the fluke's circulating cathodic antigen (CCA) in children's urine. We obtained two stool and two urine samples from 242 preschoolers in Côte d'Ivoire before and from 86 of these children after praziquantel treatment. Stool samples were examined with the Kato-Katz technique and urine samples with the POC-CCA test for S. mansoni. The sensitivity of one POC-CCA was much higher than a single Kato-Katz for S. mansoni diagnosis before (69.7% versus 28.3%) and after treatment (80.0% versus 4.0%). The POC-CCA therefore is useful for the rapid identification of S. mansoni-infected preschoolers who need treatment. The application of the POC-CCA test for monitoring of schistosomiasis control interventions needs further investigation. [ABSTRACT FROM AUTHOR]

Background: An accurate diagnosis of helminth infection is important to improve patient management. However, there is considerable intra- and inter-specimen variation of helminth egg counts in human feces. Homogenization of stool samples has been suggested to improve diagnostic accuracy, but there are no detailed investigations. Rapid disintegration of hookworm eggs constitutes another problem in epidemiological surveys. We studied the spatial distribution of Schistosoma mansoni and hookworm eggs in stool samples, the effect of homogenization, and determined egg counts over time in stool samples stored under different conditions. Methodology: Whole-stool samples were collected from 222 individuals in a rural part of south Côte d'Ivoire. Samples were cut into four pieces and helminth egg locations from the front to the back and from the center to the surface were analyzed. Some samples were homogenized and fecal egg counts (FECs) compared before and after homogenization. The effect of stool storing methods on FECs was investigated over time, comparing stool storage on ice, covering stool samples with a water-soaked tissue, or keeping stool samples in the shade. Principal Findings: We found no clear spatial pattern of S. mansoni and hookworm eggs in fecal samples. Homogenization decreased S. mansoni FECs (p = 0.026), while no effect was observed for hookworm and other soil-transmitted helminths. Hookworm FECs decreased over time. Storing stool samples on ice or covered with a moist tissue slowed down hookworm egg decay (p<0.005). Conclusions/Significance: Our findings have important implications for helminth diagnosis at the individual patient level and for epidemiological surveys, anthelmintic drug efficacy studies and monitoring of control programs. Specifically, homogenization of fecal samples is recommended for an accurate detection of S. mansoni eggs, while keeping collected stool samples cool and moist delayed the disintegration of hookworm eggs. Author Summary: An accurate diagnosis of parasitic worm (helminth) infections is important for adequate patient treatment and disease control programs. Helminth eggs in human stool samples are used as an indicator of infection intensity and morbidity. However, little is known about the exact distribution of helminth eggs in stool samples. Homogenization has been suggested to improve the diagnostic accuracy. Hookworm eggs disintegrate over time, which makes their detection challenging in epidemiological surveys. We determined the location of helminth eggs in entire stool samples from 222 individuals in Côte d'Ivoire. We also investigated whether homogenization has an effect on the detection of eggs, and determined egg counts over time in stool samples stored on ice, covered with a moist tissue, or kept in the shade. No clear pattern of helminth egg distribution was found in human stool samples. Homogenization resulted in more accurate egg counts of the blood fluke Schistosoma mansoni, while it did not affect other helminths. Keeping stool samples on ice or covered with a wet tissue slows down the disintegration of hookworm eggs. Our findings have important implications for individual patient management and the design and implementation of epidemiological surveys and helminth disease control programs. [ABSTRACT FROM AUTHOR]

Background: In sub-Saharan Africa the recommended strategy to control schistosomiasis is preventive chemotherapy. Emphasis is placed on school-aged children, but in high endemicity areas, preschool-aged children are also at risk, and hence might need treatment with praziquantel. Since a pediatric formulation (e.g., syrup) is not available outside of Egypt, crushed praziquantel tablets are used, but the efficacy and safety of this treatment regimen is insufficiently studied. Methodology: We assessed the efficacy and safety of crushed praziquantel tablets among preschool-aged children (<6 years) in the Azaguié district, south Côte d'Ivoire, where Schistosoma mansoni and S. haematobium coexist. Using a cross-sectional design, children provided two stool and two urine samples before and 3 weeks after treatment. Crushed praziquantel tablets, mixed with water, were administered at a dose of 40 mg/kg. Adverse events were assessed and graded 4 and 24 hours posttreatment by interviewing mothers/guardians. Principal Findings: Overall, 160 preschool-aged children had at least one stool and one urine sample examined with duplicate Kato-Katz thick smears and a point-of-care circulating cathodic antigen (POC-CCA) cassette for S. mansoni, and urine filtration for S. haematobium diagnosis before and 3 weeks after praziquantel administration. According to the Kato-Katz and urine filtration results, we found high efficacy against S. mansoni (cure rate (CR), 88.6%; egg reduction rate (ERR), 96.7%) and S. haematobium (CR, 88.9%; ERR, 98.0%). POC-CCA revealed considerably lower efficacy against S. mansoni (CR, 53.8%). Treatment was generally well tolerated, but moderately severe adverse events (i.e., body and face inflammation), were observed in four Schistosoma egg-negative children. Conclusions/Significance: Crushed praziquantel administered to preschool-aged children at a dose of 40 mg/kg is efficacious against S. mansoni and S. haematobium in a co-endemic setting of Côte d'Ivoire. Further research is required with highly sensitive diagnostic tools and safety must be investigated in more depth. Trial Registration: Controlled-Trials.com ISRCTN53172722 Author Summary: Schistosomiasis is a parasitic worm infection that plagues more than 200 million people in the developing world, particularly in sub-Saharan Africa. The current strategy to control schistosomiasis is to regularly administer the deworming drug praziquantel to school-aged children. Younger children before reaching school-age are not included in these deworming campaigns, because they are considered at low risk of schistosomiasis, and because the amount of available data to evaluate the safety of praziquantel in young children is insufficient. We conducted a study in two villages in southern Côte d'Ivoire and examined the stool and urine of more than 250 children (<6 years) for schistosome eggs and antigens. Children were treated with crushed praziquantel tablets (40 mg/kg) and the efficacy of this treatment was determined 3 weeks after treatment. The safety of the treatment was assessed by interviewing mothers of treated children for adverse events (e.g., abdominal pain, diarrhea, and headache). Complete data records were available for 160 children. Praziquantel cleared most of the infections. The treatment was generally well tolerated, but we observed four children who were not infected at the baseline survey who developed face and body inflammation that required close supervision by the study physician. [ABSTRACT FROM AUTHOR]

Background: Burden of disease estimates are widely used for priority setting in public health and disability-adjusted life years are a powerful "currency" nowadays. However, disability weights, which capture the disability incurred by a typical patient of a certain condition, are fundamental to such burden calculation and their determination remains a widely debated issue. Methodology: A cross-sectional epidemiological survey was conducted in the recently established Taabo health demographic surveillance system (HDSS) in south-central Côte d'Ivoire, to provide new, population-based evidence on the disability caused by schistosomiasis and soil-transmitted helminthiasis. Parasitological results from stool, urine, and blood examinations were juxtaposed to quality of life (QoL) questionnaire results from 187 adults. A multivariable linear regression model with stepwise backward elimination was used to identify significant associations, considering also sociodemographic characteristics obtained from the Taabo HDSS database. Principal Findings: Prevalences for hookworm, Plasmodium spp., Trichuris trichiura, Schistosoma haematobium and Schistosoma mansoni were 39.0%, 18.2%, 2.7%, 2.1% and 2.1%, respectively. S. mansoni and T. trichiura infections of any intensity reduced the participants' self-rated QoL by 16 points (95% confidence interval (CI): 4–29 points) and 13 points (95% CI: 1–24 points), respectively, on a scale from 0 (worst QoL) to 100 points (best QoL). The only other statistically significant effect was a 1-point (95% CI: 0.1–2 points) increase on the QoL scale per one unit increase in a calculated wealth index. Conclusions/Significance: We found consistent and significant results on the negative effects of schistosomiasis and soil-transmitted helminthiasis on adults' self-rated QoL, also when taking sociodemographic characteristics into account. Our results warrant further investigation on the disability incurred by helmintic infections and the usefulness of generic QoL questionnaires in this endeavor. Author Summary: In public health, "burden" estimates should capture the human suffering caused by certain health states, and the estimates are often used for priority setting. However, such "burden" estimates need to assess not only the number of affected people by certain conditions, but also the disability incurred by the average patient, and the determination of the degree of disability remains a widely debated issue. In order to provide new, population-based evidence on the disability caused by infections with parasitic worms, we administered a quality of life (QoL) questionnaire to 187 adults in rural Côte d'Ivoire and concurrently examined them for parasitic worm infections. We also considered sociodemographic characteristics in our analysis. In comparison with their non-infected counterparts, infected people reported a 13–16 points lower QoL on a scale from 0 (worst QoL) to 100 points (best QoL). At the same time, a one unit increase in a calculated wealth index revealed a 1-point increase in the participants' QoL. The results are consistent and warrant further investigation on the disability induced by parasitic worm infections and the usefulness of QoL questionnaires in this endeavor. [ABSTRACT FROM AUTHOR]

The final outcome of infection by Trypanosoma brucei gambiense, the main agent of sleeping sickness, has always been considered as invariably fatal. While scarce and old reports have mentioned cases of self-cure in untreated patients, these studies suffered from the lack of accurate diagnostic tools available at that time. Here, using the most specific and sensitive tools available to date, we report on a long-term follow-up (15 years) of a cohort of 50 human African trypanosomiasis (HAT) patients from the Ivory Coast among whom 11 refused treatment after their initial diagnosis. In 10 out of 11 subjects who continued to refuse treatment despite repeated visits, parasite clearance was observed using both microscopy and polymerase chain reaction (PCR). Most of these subjects (7/10) also displayed decreasing serological responses, becoming progressively negative to trypanosome variable antigens (LiTat 1.3, 1.5 and 1.6). Hence, in addition to the "classic" lethal outcome of HAT, we show that alternative natural progressions of HAT may occur: progression to an apparently aparasitaemic and asymptomatic infection associated with strong long-lasting serological responses and progression to an apparently spontaneous resolution of infection (with negative results in parasitological tests and PCR) associated with a progressive drop in antibody titres as observed in treated cases. While this study does not precisely estimate the frequency of the alternative courses for this infection, it is noteworthy that in the field national control programs encounter a significant proportion of subjects displaying positive serologic test results but negative results in parasitological testing. These findings demonstrate that a number of these subjects display such infection courses. From our point of view, recognising that trypanotolerance exists in humans, as is now widely accepted for animals, is a major step forward for future research in the field of HAT. Author Summary: The existence of a diversity of infection outcomes – ranging from self-cure to asymptomatic, severe or fatal cases – is now widely recognised for most parasitic and infectious diseases. The dogma concerning sleeping sickness, however, is still that infection is 100% fatal. Here we describe a 15-year follow-up of patients diagnosed with human African trypanosomiasis (HAT) in the Ivory Coast but who refused treatment. Our results, based on clinical, serological, molecular, and parasitological investigations, combining diagnostic tools for the field and highly specific and sensitive laboratory tests, constitute the most comprehensive study on the natural evolution of Trypanosoma brucei gambiense infection in its human host. At least two alternative natural progressions of HAT to the "classic" fatal disease were identified: a progression to an apparently aparasitaemic and asymptomatic infection and a progression to an apparently spontaneous resolution of infection. We believe that recognising that trypanotolerance exists in humans is a major step forward for future research aimed at identifying human-specific defence and immune mechanisms involved in the control of T.b. gambiense infection and thus new candidate therapeutic or prophylactic targets. [ABSTRACT FROM AUTHOR]

Background: Promising results have been reported for a urine circulating cathodic antigen (CCA) test for the diagnosis of Schistosoma mansoni. We assessed the accuracy of a commercially available CCA cassette test (designated CCA-A) and an experimental formulation (CCA-B) for S. mansoni diagnosis. Methodology: We conducted a cross-sectional survey in three settings of Côte d'Ivoire: settings A and B are endemic for S. mansoni, whereas S. haematobium co-exists in setting C. Overall, 446 children, aged 8–12 years, submitted multiple stool and urine samples. For S. mansoni diagnosis, stool samples were examined with triplicate Kato-Katz, whereas urine samples were tested with CCA-A. The first stool and urine samples were additionally subjected to an ether-concentration technique and CCA-B, respectively. Urine samples were examined for S. haematobium using a filtration method, and for microhematuria using Hemastix dipsticks. Principal Findings: Considering nine Kato-Katz as diagnostic 'gold' standard, the prevalence of S. mansoni in setting A, B and C was 32.9%, 53.1% and 91.8%, respectively. The sensitivity of triplicate Kato-Katz from the first stool and a single CCA-A test was 47.9% and 56.3% (setting A), 73.9% and 69.6% (setting B), and 94.2% and 89.6% (setting C). The respective sensitivity of a single CCA-B was 10.4%, 29.9% and 75.0%. The ether-concentration technique showed a low sensitivity for S. mansoni diagnosis (8.3–41.0%). The specificity of CCA-A was moderate (76.9–84.2%); CCA-B was high (96.7–100%). The likelihood of a CCA-A color reaction increased with higher S. mansoni fecal egg counts (odds ratio: 1.07, p<0.001). A concurrent S. haematobium infection or the presence of microhematuria did not influence the CCA-A test results for S. mansoni diagnosis. Conclusion/Significance: CCA-A showed similar sensitivity than triplicate Kato-Katz for S. mansoni diagnosis with no cross-reactivity to S. haematobium and microhematuria. The low sensitivity of CCA-B in our study area precludes its use for S. mansoni diagnosis. Author Summary: We aimed to assess the accuracy of a commercially available rapid diagnostic test for the detection of an infection with the blood fluke Schistosoma mansoni in urine. In total, 446 school children from three different settings of south Côte d'Ivoire provided three stool and three urine samples. Stool samples were examined with the widely used Kato-Katz technique and analyzed with a microscope for S. mansoni eggs. Urine samples were examined with a filtration method for S. haematobium eggs and with a rapid diagnostic test for S. mansoni that is based on detecting circulating cathodic antigens (CCA). We used a commercially available test (designated CCA-A) and an experimental formulation (CCA-B). Examination of nine Kato-Katz thick smears per child revealed a prevalence of S. mansoni in the three settings of 32.9%, 53.1%, and 91.8%. The sensitivity of triplicate Kato-Katz from the first stool sample was comparable to a single CCA-A (47.9–94.2% vs. 56.3–89.6%), and significantly higher than the sensitivity of a single CCA-B test (10.4–75.0%). CCA-A showed a considerably lower specificity than CCA-B (76.9–84.2% vs. 96.7–100%). In the settings studied in south Côte d'Ivoire, the CCA-A test holds promise for the diagnosis of S. mansoni, whereas results with CCA-B were suboptimal. [ABSTRACT FROM AUTHOR]

Background: Tsetse flies of the Palpalis group are the main vectors of sleeping sickness in Africa. Insecticide impregnated targets are one of the most effective tools for control. However, the cost of these devices still represents a constraint to their wider use. The objective was therefore to improve the cost effectiveness of currently used devices. Methodology/Principal Findings: Experiments were performed on three tsetse species, namely Glossina palpalis gambiensis and G. tachinoides in Burkina Faso and G. p. palpalis in Côte d'Ivoire. The 1×1 m2 black blue black target commonly used in W. Africa was used as the standard, and effects of changes in target size, shape, and the use of netting instead of black cloth were measured. Regarding overall target shape, we observed that horizontal targets (i.e. wider than they were high) killed 1.6-5x more G. p. gambiensis and G. tachinoides than vertical ones (i.e. higher than they were wide) (P<0.001). For the three tsetse species including G. p. palpalis, catches were highly correlated with the size of the target. However, beyond the size of 0.75 m, there was no increase in catches. Replacing the black cloth of the target by netting was the most cost efficient for all three species. Conclusion/Significance: Reducing the size of the current 1*1 m black-blue-black target to horizontal designs of around 50 cm and replacing black cloth by netting will improve cost effectiveness six-fold for both G. p. gambiensis and G. tachinoides. Studying the visual responses of tsetse to different designs of target has allowed us to design more cost-effective devices for the effective control of sleeping sickness and animal trypanosomiasis in Africa. Author Summary: Tsetse flies transmit trypanosomes causing sleeping sickness and nagana. Controlling tsetse prevents transmission of these diseases. Insecticide impregnated targets are highly effective but are too costly. This study aims to improve the cost effectiveness of targets. Experiments were performed on three tsetse species in Burkina Faso or Côte d'Ivoire. Effects of target size, shape, and the use of netting instead of black cloth were measured. We observed that targets wider than they are high (horizontal target) killed 1.6-5x more G. p. gambiensis and G. tachinoides than vertical ones. Catches were highly correlated with the size of the target up to a target size of 0.75 m, beyond which there was no further increase in catches. Replacing the black cloth of the target by netting did not change catches, but was far cheaper. Hence reducing the size of the current 1 m×1 m black-blue-black target to an horizontal 0.75×0.5 m net blue net target will improve cost effectiveness six-fold for both G. p. gambiensis and G. tachinoides. Studying the visual responses of tsetse to different designs of target has allowed us to design more cost-effective devices for the effective control of sleeping sickness and animal trypanosomiasis in Africa. [ABSTRACT FROM AUTHOR]

Background: Infections with Strongyloides stercoralis and other helminths represent important, yet often neglected issues in developing countries. Indeed, strongyloidiasis can be fatal, but only a few studies provide information regarding its health relevance in Africa. Moreover, clinical data on symptomatology and typical recognition patterns mainly originate from Western travel clinics. Methodology: A cross-sectional epidemiological survey was carried out in a rural part of south-central Côte d'Ivoire. Stool samples from 292 randomly selected individuals were examined for intestinal helminths, using a suite of diagnostic techniques (i.e., Kato-Katz, Baermann funnel, and Koga agar plate). Participants were interviewed with a pre-tested questionnaire and clinically examined. Multivariate logistic regression analysis was done to relate perceived morbidity and clinical findings to helminth infection status. Principal Findings: The prevalence of hookworm and S. stercoralis was 51.0% and 12.7%, respectively. Both infections were strongly associated with each other (adjusted odds ratio, 6.73; P<0.001) and higher prevalences were observed with age. S. stercoralis-infected individuals expressed self-reported morbidity considerably more often than those with hookworm infection. Clinical examination identified high prevalences of various pathologies and detected tendencies to worse health conditions in helminth-infected subjects. Conclusions/Significance: The use of multiple diagnostic tools showed that S. stercoralis and hookworm are co-endemic in rural Côte d'Ivoire and that each infection causes clinical symptoms and sequelae. Our findings are important for (re-)estimating the burden of helminth infections, and highlight the need for integrating epidemiological surveys, rigorous diagnostic approaches, and clinical assessments in the developing world. Author Summary: Infections with parasitic worms such as hookworm and threadworm (Strongyloides stercoralis) are widespread throughout the developing world. However, the symptoms caused by parasitic worms are unspecific and little is known about clinical presentations in endemic countries, and hence doctors' awareness of these diseases is usually low. Many infections therefore remain undetected and untreated over long time periods. As a consequence, parasitic worms can impair the well-being of infected individuals and cause harmful, sometimes even fatal health outcomes. To improve the knowledge about clinical signs and symptoms caused by parasitic worms, we administered a questionnaire to 292 children and adults in rural Côte d'Ivoire, examined them clinically, and looked at their stool for parasitic worm infections. We found that people with parasitic worms reported some symptoms, especially disorders of the gastrointestinal tract, more often than those without worms. Our clinical examination showed a trend toward worse health conditions in worm-infected people, particularly in those with S. stercoralis. Our results are important to improve patient management and control measures, and to better estimate the true health impact of parasitic worm infections. [ABSTRACT FROM AUTHOR]

Palpalis-group tsetse, particularly the subspecies of Glossina palpalis and G. fuscipes, are the most important transmitters of human African trypanomiasis (HAT), transmitting >95% of cases. Traps and insecticide-treated targets are used to control tsetse but more cost-effective baits might be developed through a better understanding of the fly's host-seeking behaviour. Electrocuting grids were used to assess the numbers of G. palpalis palpalis and G. fuscipes quanzensis attracted to and landing on square or oblong targets of black cloth varying in size from 0.01 m2 to 1.0 m2. For both species, increasing the size of a square target from 0.01 m2 (dimensions = 0.1×0.1 m) to 1.0 m2 (1.0×1.0 m) increased the catch ∼4x however the numbers of tsetse killed per unit area of target declined with target size suggesting that the most cost efficient targets are not the largest. For G. f. quanzensis, horizontal oblongs, (1 m wide×0.5 m high) caught ∼1.8x more tsetse than vertical ones (0.5 m wide×1.0 m high) but the opposite applied for G. p. palpalis. Shape preference was consistent over the range of target sizes. For G. p. palpalis square targets caught as many tsetse as the oblong; while the evidence is less strong the same appears to apply to G. f. quanzensis. The results suggest that targets used to control G. p. palpalis and G. f. quanzensis should be square, and that the most cost-effective designs, as judged by the numbers of tsetse caught per area of target, are likely to be in the region of 0.25×0.25 m2. The preference of G. p. palpalis for vertical oblongs is unique amongst tsetse species, and it is suggested that this response might be related to its anthropophagic behaviour and hence importance as a vector of HAT. Author Summary: While the numbers of cases of human African trypanosomiasis (HAT) is now less than 10,000 reported cases per year, progress against the tsetse species that spread the disease is poor, with ∼10 million square kilometres of sub-Saharan Africa still being infested. This widespread persistence of vectors and reservoir hosts threatens the long-term sustainability of recent gains against HAT. Better progress against the vector would be achieved by developing cheap, effective and practical methods of tsetse control. Toward this end, we are improving the design of insecticide-treated targets to attract and kill tsetse. Here we show that for two important vectors of HAT, Glossina palpalis palpalis in Côte d'Ivoire and Glossina fuscipes quanzensis in the Democratic Republic of Congo, small (between 0.25 m and 0.5 m square) targets of black cloth with equally sized panel of fine black netting are ∼10x more cost-effective than the larger (∼1 m square) targets or traps commonly in use. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis and soil-transmitted helminthiasis are important public health problems in sub-Saharan Africa causing malnutrition, anemia, and retardation of physical and cognitive development. However, the effect of these diseases on physical fitness remains to be determined. Methodology: We investigated the relationship between schistosomiasis, soil-transmitted helminthiasis and physical performance of children, controlling for potential confounding of Plasmodium spp. infections and environmental parameters (i.e., ambient air temperature and humidity). A cross-sectional survey was carried out among 156 school children aged 7–15 years from Côte d'Ivoire. Each child had two stool and two urine samples examined for helminth eggs by microscopy. Additionally, children underwent a clinical examination, were tested for Plasmodium spp. infection with a rapid diagnostic test, and performed a maximal multistage 20 m shuttle run test to assess their maximal oxygen uptake (VO2 max) as a proxy for physical fitness. Principal Findings: The prevalence of Schistosoma haematobium, Plasmodium spp., Schistosoma mansoni, hookworm and Ascaris lumbricoides infections was 85.3%, 71.2%, 53.8%, 13.5% and 1.3%, respectively. Children with single, dual, triple, quadruple and quintuple species infections showed VO2 max of 52.7, 53.1, 52.2, 52.6 and 55.6 ml kg−1 min−1, respectively. The VO2 max of children with no parasite infections was 53.5 ml kg−1 min−1. No statistically significant difference was detected between any groups. Multivariable analysis revealed that VO2 max was influenced by sex (reference: female, coef. = 4.02, p<0.001) and age (years, coef. = −1.23, p<0.001), but not by helminth infection and intensity, Plasmodium spp. infection, and environmental parameters. Conclusion/Significance: School-aged children in Côte d'Ivoire showed good physical fitness, irrespective of their helminth infection status. Future studies on children's physical fitness in settings where helminthiasis and malaria co-exist should include pre- and post-intervention evaluations and the measurement of hemoglobin and hematocrit levels and nutritional parameters as potential co-factors to determine whether interventions further improve upon fitness. Author Summary: The burden of parasitic worm infections is considerable, particularly in developing countries. It is acknowledged that parasitic worm infections negatively impact on children's school performance and physical development. A deeper understanding of these linkages is important for updating burden of disease measures. We investigated the relationship between worm infection status and physical fitness of 156 school children from Côte d'Ivoire and controlled for potential confounding of Plasmodium infection (the causative agent of malaria) and environmental parameters (temperature and humidity). Children were diagnosed for parasitic worm and Plasmodium infections, examined by a physician, and participated in a 20 m shuttle run test to assess their maximal oxygen uptake (VO2 max) as a proxy for physical fitness. Most of the children had parasitic worms and a Plasmodium infection. Nevertheless, their physical fitness was excellent (average VO2 max: 52.7 ml kg−1 min−1). The level of VO2 max was only influenced by sex and age, but not by parasitic worms and Plasmodium infections. In future studies, the dynamics of children's physical performance should be assessed before and after control interventions, including the assessment of blood hemoglobin, hematocrit, and nutritional indicators to determine whether physical fitness in worm- and Plasmodium-infected individuals can be further improved. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU), is unique among human pathogens in its capacity to produce a polyketide-derived macrolide called mycolactone, making this molecule an attractive candidate target for diagnosis and disease monitoring. Whether mycolactone diffuses from ulcerated lesions in clinically accessible samples and is modulated by antibiotic therapy remained to be established. Methodology/Principal Finding: Peripheral blood and ulcer exudates were sampled from patients at various stages of antibiotic therapy in Ghana and Ivory Coast. Total lipids were extracted from serum, white cell pellets and ulcer exudates with organic solvents. The presence of mycolactone in these extracts was then analyzed by a recently published, field-friendly method using thin layer chromatography and fluorescence detection. This approach did not allow us to detect mycolactone accurately, because of a high background due to co-extracted human lipids. We thus used a previously established approach based on high performance liquid chromatography coupled to mass spectrometry. By this means, we could identify structurally intact mycolactone in ulcer exudates and serum of patients, and evaluate the impact of antibiotic treatment on the concentration of mycolactone. Conclusions/Significance: Our study provides the proof of concept that assays based on mycolactone detection in serum and ulcer exudates can form the basis of BU diagnostic tests. However, the identification of mycolactone required a technology that is not compatible with field conditions and point-of-care assays for mycolactone detection remain to be worked out. Notably, we found mycolactone in ulcer exudates harvested at the end of antibiotic therapy, suggesting that the toxin is eliminated by BU patients at a slow rate. Our results also indicated that mycolactone titres in the serum may reflect a positive response to antibiotics, a possibility that it will be interesting to examine further through longitudinal studies. Author Summary: Mycolactone is a diffusible cytotoxin produced by Mycobacterium ulcerans, the causative agent of the skin disease Buruli ulcer. In a previous study using animal models, we reported that mycolactone released by cutaneous foci of infection gains access to the peripheral blood. Here we investigated whether mycolactone circulates in human patients and is detectable in clinically accessible samples. Using a combination of solvent extraction, high performance liquid chromatography and mass spectrometry analysis, we found that structurally intact mycolactone was present in ulcer exudates obtained from wound swabs and in the serum of patients. Unexpectedly, high titres of mycolactone were detected in ulcer exudates after completion of antibiotic treatment. In contrast, mycolactone could only be detected in the serum of newly diagnosed patients. Our results demonstrate that mycolactone detection in serum and ulcer exudates may be used to diagnose BU. Moreover, they suggest that the kinetics of mycolactone concentration in serum may be indicative of the clinical response of patients to antibiotic therapy. [ABSTRACT FROM AUTHOR]