Neglected tropical diseases in Republic of Guinea: disease endemicity, case burden and the road towards the 2030 target

Abstract Neglected tropical diseases (NTDs) predominantly affect vulnerable and marginalized populations in tropical and subtropical areas and globally affect more than one billion people. In Guinea, the burden of NTDs is estimated to be >7.5 disability-adjusted life years per million inhabitants. Currently the Guinea NTDs master plan (2017–2020) has identified eight diseases as public health problems: onchocerciasis, lymphatic filariasis, trachoma, schistosomiasis and soil-transmitted helminthiasis, leprosy, human African trypanosomiasis and Buruli ulcer. In this review we discuss the past and the current case burden of the priority NTDs in Guinea, highlight the major milestones and discuss current and future areas of focus for achieving the 2030 target outlined by the World Health Organization.


Introduction
Neglected tropical diseases (NTDs) predominantly affect vulnerable and marginalized populations in tropical and subtropical areas and globally affect more than one billion people. 1 To prevent and control NTDs, the World Health Organization (WHO) launched its first road map in 2012. 2 Substantial gains made in the last decade include 500 million fewer people requiring interventions against NTDs in 2020 compared with 2010 and 40 countries, territories and areas have eliminated at least one NTD. 1 The 2020 WHO road map built on the achievements of the first WHO road map has outlined several targets to be achieved by the year 2030. 1 The overarching target is to achieve a 90% reduction in the number of people requiring interventions against NTDs, for at least 100 countries to eliminate at least one NTD, to eradicate two diseases (yaws and guinea worm) and to achieve a 75% reduction in the disability-adjusted life years (DALYs) related to NTDs. 1 In Guinea, the National Programme for the Control of NTDs was launched in 2018 and drafted the Guinea NTDs master plan (2017-2020) to combat eight NTDs that were considered a public health problem: onchocerciasis, lymphatic filariasis (LF), trachoma, schistosomiasis and soil-transmitted helminths (STHs), leprosy, human African trypanosomiasis (HAT) and Buruli ulcer (BU). 3In addition to the recognisable burden of malaria and high neonatal mortality, 4 -6 Guinea also bears a substantial burden of NTDs, with an estimated 7.5 DALYs per million inhabitants attributed to NTDs. 1 , 7 In this review we discuss the past and the present situation of the eight NTDs identified by the Guinean national control program along with other emerging or existing infections, highlight International Health major milestones and discuss current and future areas of focus for achieving the 2030 target.

Onchocerciasis (river blindness)
Onchocerciasis is a major infectious cause of blindness in the world.The Onchocerciasis Control Programme in West Africa (OCP), launched in 1974, has led to a steady decline in the global burden of the disease.The OCP initially began in seven countries (Benin, Burkina Faso, Cote d'Ivoire, Ghana, Mali, Niger and Togo) with the objective of eliminating onchocerciasis as a disease of public health concern.Prior to Guinea joining the OCP in 1986, the transmission was hyperendemic, with a very high disease prevalence ( > 60% prevalence in Upper Guinea in the 1980s and 20 000 blind people). 3 , 8A large-scale survey carried out in late 1980s as part of the OCP estimated a high burden of onchocerciasis; 14 villages in Guinea were identified as hyperendemic, with an overall disease prevalence of 65% and blindness prevalence of 6.5%. 9 , 10In order to reduce the burden of the disease, implementation of the OCP in Guinea began in 1987 and the program ran until 2002 in two distinct phases.During the first phase (1987-1997), larviciding was carried out and ivermectin treatment was administered by a mobile team of health workers.This combined use of vector control and ivermectin led to a rapid interruption of transmission. 11In the second phase (1997-2002), the control activities focused on larviciding under community-directed treatment with ivermectin (CDTI).From 2002 onwards, control activities have been implemented under CDTI.
The success of the OCP has led to a reduction in the prevalence of onchocerciasis in Guinea from 43-88% during the period of hyperendemic transmission to 0-15% in 2002. 3From 2003, the fight against onchocerciasis and other causes of blindness, including trachoma, were merged into a single program called the National Onchocerciasis and Blindness Control Program (PNLOC).To sustain the control activities, 2 570 255 Guineans received ivermectin treatment in 2009.Although the disease was considered endemic in Guinea until 2015, 12 onchocerciasis is now no longer a major public health concern in the country .A recent modelling study has indicated a high environmental suitability index for disease transmission in most regions of Guinea expect the western coastal regions. 13Guinea has just completed mass drug administration (MDA) with ivermectin in 23 of 38 districts, with the last round completed in September 2022.The overall target is to achieve elimination by 2030.

LF (elephantiasis)
In Guinea, the LF elimination program was initiated in 2000 after the WHO launched its global elimination program. 14A survey carried out across 46 sites in 2005 found a median disease prevalence of 0.5% (range 0.0-23.0). 15In 2013 the NTDs master plan reported a prevalence of circulating filarial antigens of Wuchereria bancrofti to be between 4.5 and 46.3% and a microfilariae prevalence of 3.0-6.7%. 16There has been a gradual reduction in the prevalence of LF in the past 2 decades: the estimated prevalence was 2-5% during 2000-2010 and < 2% during the period 2010-2018. 17In 2013, 0.5% of the total population required preventative chemotherapy. 18MDA activities have been highly successful, with achievement of 100% geographic coverage in 2020. 19Resistance to permethrin and deltamethrin has been identified in Faranah and can be a challenge for the vector control activities. 20urrently a transmission assessment survey (TAS) is being undertaken.In 2022, the first assessment (pre-TAS) survey was conducted in 10 districts, with an overall prevalence observed of 0.0-0.43%.During the NTDs annual review workshop, which took place on 26-28 December 2022, it was reported that 11 districts underwent pre-stop surveys (TAS1), with an overall prevalence estimated at 0-5.4% (personal communication, Michel Sagno).

Blinding trachoma
Guinea was one of the five countries that accounted for nearly half of the global burden of active trachoma. 21In 2011, the disease prevalence among children < 10 y of age was 33% in a large nationwide survey. 3Most of the surveys conducted during the 2010-2019 period indicated an overall disease prevalence of < 5% in most of the survey locations, expect in Faranah and Dinguiraye, which had a high prevalence of 30.0-49.9% in 2011. 22he country has implemented several components of the WHOsupported SAFE (surgery for treatment of advanced cases, antibiotics for follicular stage, facial cleanliness and environmental improvement) strategy since 2004.MDA with azithromycin and tetracycline ophthalmic ointment (preventive chemotherapy) began in 2013 and covered the nine health districts of the Upper Guinea region where the prevalence of follicular trachoma is > 10%.A target date of 2015 was set for elimination of blinding trachoma. 2However, trachoma is still endemic in 31 of the 38 health districts and 3.6 million people required treatment in 2018. 23National trachoma mapping surveys (27 surveys) were conducted during 2011-2016, which reported an adjusted prevalence of trachomatous inflammation-follicular (TF) that ranged from 1.0 to 41.8%, while the adjusted point prevalence of trachomatous trichiasis (TT) ranged from 0.0 to 2.8% and an estimated 32 737 individuals required TT surgery. 24The fight against trachoma is a major priority for the national control program, especially in the Upper Guinea region and the northern part of Middle Guinea, where the disease prevalence remains high.

Schistosomiasis (bilharzia)
Schistosomiasis has been a major public health problem in Guinea, with different surveys carried out between the 1930s and 1980s indicating a high prevalence of the disease (see Table 1 ).In Guinea, it is present in two major forms: the urinary disease caused by Schistosoma haematobium and the intestinal disease caused by Schistosoma mansoni .Transmission risk is high throughout the country, especially in the Upper Guinea region, where rice farming provides a suitable niche for the intermediate host (snail). 25In 1995, the prevalence of S. mansoni and S. haematobium among schoolchildren was 25% and 19.9%, respectively. 26In a survey carried out a decade later (2009-2010), the disease prevalence ranged from 23.5% to 49.6% for S. haematobium and 30.2% to 47.5% for S. mansoni . 3During 1996-2007, praziquantel, mebendazole, iron and folic acid donated by the WHO and the World Bank were the cornerstone   27 Currently, all 38 districts are endemic for the disease.

Leprosy
Leprosy, a disease caused by Mycobacterium leprae , predominantly affects the skin and the peripheral nerves and can lead to long-term disabilities.The disease is associated with stigma, especially when deformities are present.In 1988 the prevalence was 1.2% in Pita, a town in Fouta Djallon, Middle Guinea. 30In 1990 the prevalence of leprosy was nearly 12 cases per 10 000 inhabitants. 3 A leprosy elimination campaign was organised in 1997 with the launch of several targeted programs.Overall, leprosy control has been based on screening of cases in all health centres, treatment of the identified cases, awareness and sensitisation campaigns and the establishment of reference centres for diagnosis and management of cases. 31This led to achieving the elimination target ( < 1 case per 10 000 residents) in all 38 health districts. 3The overall country prevalence was 0.58 cases per 10 000 inhabitants in 2008 31 and 0.21 cases per 10 000 inhabitants in 2014.Since 2002, the case detection system remains passive and in high-prevalence villages, leprosy days are organised.The disability percentage among incident cases remains high (9% in 2008). 3Recently, dapsone-and rifampicin-resistant leprosy has been identified; 32 this is a major concern as treatment options for resistant cases are limited.Currently all the districts have reached the threshold of leprosy elimination (i.e.< 1 case per 10 000 inhabitants). 31However, there are still hyperendemic areas with more than one case in some districts.A large proportion of the cases (86%) are multibacillary. 31The proportion of children among new cases was approximately 10% in 2008 and 7% in 2017; 31 the proportion of mutilated among new cases was 17%, with an overall disease prevalence of 0.23 per 10 000 inhabitants in 2017.More than 9% of the patients screened have a degree 2 disability according to the WHO scale. 31

HAT (sleeping sickness)
HAT is caused by the parasite Trypanosoma brucei , which is transmitted by tsetse flies belonging to the genus Glossina .Two subspecies of T. brucei are pathogenic for humans: T. b. gambiense and T. b. rhodesiense .In West Africa, HAT is caused by the former species. 33The number of HAT cases decreased by 95% between 2000 and 2018 and the WHO has targeted to interrupt transmission of the disease (to zero cases) by 2030. 34uinea has the largest number of HAT cases observed among West African countries.A total of 7.5% of the Guinean land area is considered at risk for T. b. gambiense and this translates to nearly 25% of the population living at risk. 35Transmission occurs mainly in the coastal regions with mangrove ecosystems (e.g.Boffa prefecture has the highest incidence in Guinea), as rice culture and attendance of pirogue jetties are associated with higher transmission risk. 33 , 36Annually there have been < 150 cases reported to the WHO for the past 3 decades; the burden used to be much higher in the earlier half of the 20th century. 37The 2014-2015 Ebola virus disease (EVD) outbreak deeply impacted HAT control activities, with a direct impact on its surveillance and diagnosis; this led to an increase in the DALYs burden of at least 150. 38Subsequent intensification of activities has led to a decline in cases. 39he elimination target is likely to be achieved, as the National Sleeping Sickness Control Programme has been carrying out integrated vector control and medical intervention activities in collaboration with the Trypa-NO!partnership. 39 , 40ajor challenges remain in the elimination of the disease from the regions with mangrove systems that harbour the main vector for transmission ( Glossina palpalis gambiensis ). 33 , 41Skin, a potential reservoir that has been previously unaccounted for, may need to be considered as a part of future control activities as the elimination goal is closer to being realised. 42

BU
BU is a chronic debilitating disease caused by Mycobacterium ulcerans .The exact mode of transmission to humans is unknown.Most of the cases are observed in children < 15 y of age in West and Central Africa.The disease causes long-term disability in an estimated 25% of those affected. 43The history of BU in Guinea is relatively unknown, although its presence prior to 1980 has been reported in the literature, with further reported in 1995. 44The disease is currently endemic in Guinea and several areas of the country, especially the coastal regions in the western part, are predicted to be suitable for BU. 45 , 46 From 2002 to 2018, a total of 1582 cases were reported to the WHO by the Guinean health services, with 102 cases reported in 2018, 47 including 10 cases confirmed by polymerase chain reaction (PCR) In 2010. 31During 2014-2017, active screening and treatment of 348 cases were undertaken.The Guinean government has identified 3 of the 38 health districts as being suspected endemic. 3he control of BU has relied on early community-based detection and comprehensive care of patients to break the chain of transmission. 31As a part of the control program, doctors have been trained in case identification and management and a screening and treatment centre was established in N'Zérékoré in 2005.Guinea was one of the participating countries of the 2009 Cotonou Declaration. 48A recent study that classified any case of International Health chronic cutaneous ulcer as BU reported a total of 389 cases in 2018, 400 cases in 2019 and 222 cases in 2020, with a wide geographic distribution of cases. 49The main target for 2030 outlined in the NTD road map 2021-2030 is to reduce the proportion of cases diagnosed in category III (severity grade) from 30% (baseline) to < 10%. 43Diagnosis remains a major challenge, as samples for confirmatory PCR need to be sent to Cote d'Ivoire, leading to delayed case confirmation. 49

Snakebite envenoming (SE)
The burden of SE prior to the 2000s remains unclear, with only a handful of annual deaths reported in the 1950s. 50In 2005 there were 6 million people at risk of SE and a total of 8000 cases were treated (Table 2 ). 51A global mapping study in 2018 estimated that 518 883 people were at risk of exposure to one or more venomous snake species and 427 253 were at risk of exposure to a snake for which no effective therapy exists. 52The following venomous snake species are found in Guinea: Atheris chlorechis (West African bush viper), Bitis arietans (puff adder), Bitis nasicornis (rhinoceros viper), Bitis rhinoceros (West African gaboon viper), Dendroaspis polylepis (black mamba), Dendroaspis viridis (western green mamba), Dispholidus typus (boomslang), Echis jogeri (Joger's carpet viper) and Naja katiensis (West African brown spitting cobra). 53A fifth of the envenomations are due to elapids and the case fatality rate ranges from 15% to 27%. 54nnually SE leads to 159 (95% CI 126 to 193) deaths and 192 (95% CI 118 to 327) amputations, with the DALYs burden estimated at 11 344 (95% CI 8800 to 14 296). 55The unavailability of antivenom and high treatment cost remains a major problem throughout the country, expect in Kindia-a region with one of the highest reported incidences of snakebites in the world. 51 , 56At the only dedicated snakebite clinic in Guinea, located in the Kindia region, approximately 700 cases are reported annually. 57However, the actual number of cases is likely to be underestimated, as many people may not seek treatment due to the potential financial burden. 57

Scorpion envenoming
The burden of scorpion envenoming remains unknown but is considered to be highly underreported; a case series described 75 cases during 2010-2012 in Conakry. 58Mortality is considered to be lower than that from SE. 59

Dengue
Currently there is a moderate level of evidence of the presence dengue virus (DENV) in Guinea 60 and low-intermediate transmission risk. 61DENV serotype 2 was reported in 1981 62 and in 1996, 63 and a case was identified in Faranah in 2006. 64Aedes aegypti mosquitoes, the primary vector for dengue transmission is present in Guinea. 65A modelling study in 2010 estimated a mean number of apparent cases of 192 067 (2.5th to 97.5th: 125 712 to 275 871); an apparent infection was defined as an infection with sufficient severity to modify a person's regular schedule. 18 , 66part from the sporadic case reports, there is relatively little information regarding the epidemiology of DENV in Guinea (Table 2 ).

Chikungunya
There is good consensus on the presence of chikungunya virus (CHIKV) in Guinea, with high environmental suitability for transmission of the virus. 67A CHIKV outbreak occurred in 1992 68 and eight confirmed/suspected cases of CHIKV were reported in 2006. 64There are no recent reports on CHIKV, although outbreaks were documented in neighbouring Senegal in 2015 69 and Sierra Leone in 2012. 70

Yaws
Guinea was endemic for yaws in the 1940s, with a total of 32 900 cases identified in 1948. 71Mass treatment campaigns in the 1950s and 1960s led to a global decline in the burden of yaws by 95%. 72However, there was a resurgence in Africa after curtailment of control activities in the 1970s and 1980s.A total of 1232 cases were reported to the WHO during 1974-1976, 73 with a further 789 cases reported in 1977-1982. 74In 2019, the disease was identified in a wild chimpanzee in the Sangaredi area. 75hile the disease was previously endemic in the country, the current status remains unknown.

Mycetoma
Despite Guinea falling within the 'mycetoma belt', 76 the burden of the disease remains unknown.Description of the disease is limited to case reports among citizens living aboard.In 2010, two cases of mycetoma were reported in Guinean females. 77Another case report described eumycetoma caused by Exophiala jeanselmei in a 29-year old Guinean woman (resident in France for the last 10 y)-the infection could have been acquired in Guinea through percutaneous contamination. 78

Taeniasis
Taenia solium is suspected to be endemic in 2018, with a pig population of 104 000, including the practice of backyard pig produc tion. 79Infec tion with T. solium (pork tapeworm) can cause the intestinal infection taeniasis, which has no major impact on human health.Ingestion of T. solium eggs via the faecal-oral route or by ingesting contaminated food or water causes infection in humans with the larval parasite in muscles, skin, eyes and the central nervous system (human cysticercosis).Taenia spp.were identified in 3.8% of the schoolchildren in a national survey in 1995 (species were not described). 26

Rabies
Guinea has one of the largest burdens of human rabies, with a mortality rate of more than three deaths per 100 000 population. 82Nearly 8000 incidents of animal bites were reported in Conakry during an 11-y study period (2002-2012). 83

Yellow fever
Outbreaks of yellow fever have been reported between 2006 and 2010, with a total of 80 cases identified, including 74 confirmed cases during an outbreak in 2005. 84Four suspected cases of yellow fever were reported from the Faranah region (in January-February 2022; immunoglobulin M negative eventually).There was one confirmed case identified in December 2022 (Faranah region); two suspected cases were reported in January 2023 (Faranah region; waiting for diagnostic confirmation) (personal communication, MSC).The disease is transmitted by A. aegypti , which is widely abundant in Guinea.

Discussion
Guinea has implemented several programs to combat NTDs in the past 50 y.Major achievements during this period include certification of the eradication of dracunculiasis in 2009, 80 , 81 the absence of confirmed reports of yaws in recent years 85 and onchocerciasis is no longer considered a major public health concern. 12radication of yaws and dracunculiasis is one of the objectives of the WHO 2030 roadmap, and Guinea is well-positioned to achieve this.As part of a synergistic action and pooling of resources, the Ministry of Health decided in 2018 to group all NTDs into a single program called the National Program for the Fight Against NTDs.Some of the lessons learned from this program have been applied in the development of the revised NTDs master plan (2019-2023).A prior evaluation was carried out to review progress, identify common challenges and explore further opportunities for an integrated coordination of activities. 31nterrupting the transmission of STHs is considered highly unfeasible in Guinea and therefore STHs will continue to be a major NTD for the foreseeable future. 29Recently, dapsone-and rifampicin-resistant leprosy has been identified in a study among 24 patients. 32This is a major concern, as there are limited alternatives for the treatment of rifampicin-resistant cases.Despite the impressive control of trachoma, elimination of the disease from regions with mangrove systems currently remains a main challenge. 33 , 41Active screening and effective implementation of vector controls can help in achieving the zero transmission target by 2030. 86AT is likely to meet the 2030 target of zero transmission; active screening of cases to tackle the human reservoir and effective implementation of tsetse fly vector control measures remain the key. 86 , 87The development of fexinidazole as an oral treatment for both the stages of HAT is an important development 88 ; effective treatment compliance might be the key. 89The number of HAT cases is generally low and the burden appears to be mostly in the coastal region.Targeted active surveillance will lead to early identification of patients in stage 1, as passively diagnosed patients are more likely to present with later stages of the disease. 90The recent identification of skin as a potential reservoir needs to be considered as a part of future control activities for HAT. 42here are also further immediate challenges that threaten the different NTD programs: recurrent EVD outbreaks, the rampant use of counterfeit medicines and the ongoing coronavirus disease 2019 (COVID-19) pandemic.Unlike EVD outbreaks, which remain relatively localised, the ongoing COVID-19 pandemic has disrupted programs throughout the country.Guinea was one of the first countries in Africa to resume its MDA program during the COVID-19 pandemic without causing an observed increase in transmission. 91The resumption of activities coincided with the rainy season, and poor road conditions could have impeded the implementation progress. 92ales of counterfeit medicines occur regularly despite the government's crackdown. 93 , 94According to government officials, > 100 000 deaths per year are thought to be due to fake or falsified drugs. 95Despite a high burden attributed to counterfeit and substandard medicines, it remains largely neglected.Lessons learned from the cross-border collaboration (Mano River union) between Sierra Leone, Liberia, Guinea and Ivory Coast to combat onchocerciasis in West Africa can be useful. 96More of such initiatives are required to combat the NTDs in the region, as several diseases, such as HAT, have resurfaced after initial success in the 1960s, 37 therefore sustained and coordinated control activities remain important.
Finally, only eight diseases are currently identified as major public health concerns in the Guinean NTDs master plan.Several diseases with a high burden currently remain underrecognised.For example, Guinea has a large burden of rabies, with mortality of more than three deaths per 100 000 population, 82 and SE is clearly an underrecognised problem, 52 especially in the Kindia region. 97The control program should consider including these NTDs as part of the national surveillance program.

Conclusions
Guinea has made important progress towards combating NTDs, especially against yaws, dracunculiasis, onchocerciasis, trachoma and leprosy.Combatting NTDs through nationally coordinated efforts while dealing with the epidemic threats posed by viral illnesses should be a national priority.

Table 1 .
Eight NTDs listed in the Guinean NTDs program priority list

Table 2 .
NTDs that are currently not on the priority list of the Guinean NTDs program