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Acta Tropica 175 (2017) 91–99

Contents lists available at ScienceDirect

Acta Tropica

jo ur nal home p age: www.elsev ier .com/ locate /ac ta t ropica

reatment of human and livestock helminth infections in a mobileastoralist setting at Lake Chad: Attitudes to health and analysis ofctive pharmaceutical ingredients of locally available anthelminthicrugs

elena Gretera,b, Noemi Cowana,b, Bongo N. Ngandoloc, Hamit Kesselyd,driss O. Alfaroukhc, Jürg Utzingera,b, Jennifer Keisera,b, Jakob Zinsstaga,b,∗

Swiss Tropical and Public Health Institute, Basel, SwitzerlandUniversity of Basel, Basel, SwitzerlandInstitut de Recherche en Elevage pour le Développement, N’Djamena, ChadCentre de Support en Santé International, N’Djamena, Chad

r t i c l e i n f o

rticle history:eceived 12 December 2015eceived in revised form 23 May 2016ccepted 24 May 2016vailable online 25 May 2016

eywords:nthelminthic drugshadascioliasisocus group discussionobile pastoralists

chistosomiasis

a b s t r a c t

Mobile pastoralists face challenges in accessing quality health care and medication for managing humanand animal diseases. We determined livestock disease priorities, health seeking behaviour of peoplebearing helminthiases and − placing particular emphasis on trematode infections − treatment strate-gies and outcome satisfaction among mobile pastoralists of four ethnic groups in the Lake Chad areausing focus group discussions. People suffering from schistosomiasis were interviewed about symptoms,health seeking behaviour and their satisfaction with respect to the provided treatment. Anthelminthicdrugs for human and veterinary use obtained from various health care structures were analysed for activepharmaceutical ingredients (API) and quantity, using high pressure liquid chromatography-UV and liquidchromatography combined with tandem mass spectrometry. Most people suffering from schistosomia-sis sought treatment at health care centres. Yet, they also consulted informal providers without medicaltraining. Regarding animal health, self-mediated therapy was common to manage suspected livestockfascioliasis. Self-reported treatment satisfaction for human schistosomiasis and trematodiasis treatmentoutcome in livestock were low. Mobile pastoralists perceived the purchased drugs to be of low quality.Among 33 products locally sold as anthelminthic drugs for human or veterinary use, 27 contained alben-dazole or mebendazole, varying between 91% and 159% of the labelled amount. Six products were soldloosely with incomplete information and their API could not be identified. No counterfeit anthelminthic

drugs were detected. None of the samples contained praziquantel or triclabendazole, the drugs of choiceagainst schistosomiasis and fascioliasis, respectively. The perceived unsatisfactory treatment outcomes inhumans and animals infected with trematodes are most likely due to empiric diagnosis and the resultinguse of inadequate therapy for human schistosomiasis and the lack of efficacious drugs against livestock fascioliasis.

. Introduction

Parasitic worm infections cause a considerable burden inumans and livestock, particularly in tropical and sub-tropical

egions of the world (Hotez et al., 2014; Karagiannis-Voulest al., 2015; Torgerson et al., 2015). In humans, soil-transmittedelminths (Ascaris lumbricoides, hookworm and Trichuris trichiura)

∗ Corresponding author at: Swiss Tropical and Public Health Institute, P.O. Box,H-4002 Basel, Switzerland.

E-mail address: jakob.zinsstag@unibas.ch (J. Zinsstag).

ttp://dx.doi.org/10.1016/j.actatropica.2016.05.012001-706X/© 2016 Elsevier B.V. All rights reserved.

© 2016 Elsevier B.V. All rights reserved.

and Schistosoma spp. infections are widespread, mainly in settingswhere open defecation is common (Grimes et al., 2014; Strunzet al., 2014). Various intestinal helminths (e.g. Haemonchus spp.,Trichostrongylus spp., Ancylostoma spp., Trichuris spp. and Strongy-loides spp.) parasitise ruminant livestock (Zinsstag et al., 1998).Of zoonotic importance are Echinococcus spp., Taenia spp. and thetrematode species Fasciola hepatica and F. gigantica, which mayaccidentally infect humans (Fürst et al., 2012; Garcia et al., 2007).

Livestock might also suffer from infection with the blood flukeSchistosoma bovis (Moné et al., 1999).

92 H. Greter et al. / Acta Tropica 175 (2017) 91–99

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Fig. 1. Drugs for human and veterinary use on display in a villa

Low-intensity infections may remain undiagnosed, explainedy the absence or unspecific symptoms, coupled with insensitiveiagnostic methods (Becker et al., 2015; Bergquist et al., 2009). Yet,hronic intestinal helminth infections can cause considerable mor-idity (Hotez et al., 2014). Parasitic infections not only compromiseealth, but also cause economic losses due to reduced productiv-

ty of livestock, weight loss and higher rates of abortion (Charliert al., 2014). Hence, helminthiases have a double negative impactn populations which depend on livestock, such as settled livestockreeders and mobile pastoralists (Bechir et al., 2011; Charlier et al.,014).

Safe and efficacious drugs are available for most intestinalelminth infections (Panic et al., 2014). Regarding human health,he global strategy for the control of major helminthiases isuilt around preventive chemotherapy, which is the periodiceworming of at-risk populations coordinated by the World Healthrganization (WHO). For example, 600 million tablets of albenda-ole and mebendazole are donated yearly to deworm school-agedhildren. Schistosomiasis is on the WHO agenda for elimination as

public health problem by 2025 (WHO, 2013), and praziquantel ishe drug of choice (Doenhoff et al., 2008; WHO, 2002). The afore-

entioned drugs are also used in veterinary medicine (Mehlhorn,008). For fascioliasis in livestock and humans, triclabendazole ishe recommended treatment (Keiser et al., 2005; Villegas et al.,012).

In grassland ecosystems such as the Sahelian belt of Africa,obile pastoralism is a highly adapted lifestyle that largely depends

n livestock and allows maintaining human populations on onlyarginally productive land. Mobility is key, driven by the constant

earch for water and appropriate pasture (Krätli and Schareika,010). Camels, cattle, goats and sheep provide milk and meator consumption and trade and are often referred to as “a bankn four legs” by the pastoralists. Hence, animal health is crucial,ince the health of the people is directly dependent on healthynd productive animals (Bechir et al., 2012). However, to date,ccess to health care is often limited for rural populations in

ow- and middle-income countries, particularly for marginalisednd mobile populations (Obrist et al., 2007; Sheik-Mohamed andelema, 1999; Sy et al., 2010; Wiese et al., 2004; Zinsstag et al.,

rket in the Lake Chad area in May 2014 (photo: Helena Greter).

2006). In resource-constrained settings, health systems often lackadequate governmental funding and sufficient qualified person-nel. Consequently, health posts in rural areas are sparse and asingle health post may represent the only official health providerfor more than 10,000 people. Additionally, health centres in ruralareas are characterised by a lack of basic infrastructure, clean waterand sufficient space for inpatients. Shortages in life saving medica-tions are common. With regard to veterinary health, the situationis comparable and governmental veterinary services infrequentlycover vaccination services (Schelling et al., 2007). In Chad, theprivate sector stepped in to fill the gap and developed business-oriented health services. An informal market for drugs has evolvedand medical products are available in city and village markets andfrom street vendors (Videau, 2006), as shown in Fig. 1. However,sales persons are untrained, thus a purchase from these sourcesis not accompanied by any kind of guidance on the treatment.The origin and quality of the sold drugs are often unknown sincethese products might be imported into Chad via unofficial routes,presumably without maintaining quality guidelines of the pharma-ceuticals, such as storage temperature. This practice has establishedin the 1990s in Chad and − despite its non-authorised status −continues to build inroads, since purchase from these sources isrelatively straightforward and inexpensive (Djimouko and Mbairo,2014). In the Lake Chad area, doctor choukou (i.e. unqualified salespersons who offer drugs for human and veterinary use and ser-vices such as infusions and injections) travel from camp to campto serve the needs of the mobile pastoralists. Since doctor choukoulack medical training, the drugs and treatments provided by themmight cause harm in humans and animals (Djimouko and Mbairo,2014; Gauthier and Wane, 2011; Hampshire, 2002; Schelling, 2002;Wiese, 2000).

The aim of the current study was to elucidate mobile pastoral-ists’ perception of schistosomiasis, livestock disease priorities andaccess to, and common practice of, treatment of human and ani-mal helminth infections on the south-eastern shores of Lake Chad.Additionally, medications locally sold as anthelminthic drugs for

human or veterinary use were purchased and tested for the pres-ence and quantity of active pharmaceutical ingredients (API) as ameasure for anthelminthic drug quality.

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. Materials and methods

.1. Ethical considerations

The study was approved by the ethics committee of Basel,witzerland (reference no. EKBB 64/13) and the ‘Direction Généralees Activités Sanitaires’ in N’Djamena, Chad (reference no.43/MSP/SE/SG/DGAS/2013). At the first contact with each group ofobile pastoralists, the objectives and procedures were explained.

he group leader, together with other local authorities, had time toiscuss and decide about the groups’ participation. Once a collectiveecision had been taken, written informed consent was obtainedrom the group leader. Due to high illiteracy rates, individual partic-pants consented orally. These consent procedures were approvedy the respective ethics committees.

.2. Study site and study population

The study was carried out between September 2013 and May014 and focussed on 19 individual groups of mobile pastoralists,

ocated on the south-eastern shores of Lake Chad. Participating pas-oralists were of four different ethnic groups; Gorane, Arab, Fulanind Buduma. Due to the longstanding research partnership withastoralist communities in the study area (Montavon et al., 2013),he sampling of the groups was partly convenience (10 groups) andartly random (nine groups), by contacts along transects.

.3. Qualitative data collection

Within each of the 19 participating groups, 20 individuals aged years and above were randomly selected for a parasitologicalurvey, examining urine and stool samples. All human partici-ants diagnosed with helminths received treatment administeredy a study nurse, following national guidelines. Individuals iden-ified with a Schistosoma infection were interviewed using a shortre-tested questionnaire addressing standard questions on diseaseerception and duration, health seeking behaviour and treatmentutcomes (Lengeler et al., 2002a, 2002b). For children below thege of 10 years, parents or legal guardians were interviewed. Addi-ionally, seven individuals with symptoms that might be due tochistosomiasis who had contacted the study nurse were identi-ed as positive for Schistosoma infection and participated in theuestionnaire interview.

Focus group discussions (FGDs) were conducted to address ani-al health topics. People responsible for livestock were eligible

o participate, depending on their availability at the time of theisit. These FGDs comprised three to six adult individuals and top-cs addressed included animal health priorities and health seekingehaviour. In groups reporting fascioliasis as a priority, treatmenttrategies and outcome satisfaction were discussed. Languagessed for the questionnaire interviews and the FGDs were Chadianrabic, Kanembu and Fulbe. An interpreter translated questionsnd answers into French for the investigator. The content of theseranslations were validated with a second independent interpreter.

.4. Purchase of locally available anthelminthic drugs

Between September 2014 and March 2015, two Chadian col-aborators purchased locally available anthelminthic drugs fromarious outlets, namely village markets, health centres and infor-

al drug sellers (doctor choukou) in the study area, as well as in

uman and veterinary pharmacies and on markets in N’Djamena.ollaborators asked for drugs to treat human helminthiasis andnimal fascioliasis, using local language terms.

a 175 (2017) 91–99 93

2.5. API content analysis of anthelminthic drugs

2.5.1. Reagents and apparatusAlbendazole, mebendazole, thiabendazole, flubendazole

(Sigma-Aldrich; Buchs, Switzerland) and triclabendazole (Carbo-gen Amics; Bubendorf, Switzerland) were of analytical standard.Methanol, acetonitrile and 25% hydrochloric acid were of highpressure liquid chromatography (HPLC)-grade. An Agilent Series1100 HPLC-UV/vis system with computer control (ChemStation)was used for the chromatographic analysis of albendazole, meben-dazole, thiabendazole and flubendazole. For the tandem massspectrometric measurements of triclabendazole and praziquantel,an API 3000 triple quadrupole mass spectrometer (MS) (AB Sciex;Framingham, MA, USA) with a turbo inspray interface was used.

2.5.2. Standard solutions and calibration lineThe preparation of the drug solution was adapted from Kulik

et al. (2011). Briefly, albendazole and mebendazole were dis-solved in 0.25% hydrochloric acid in methanol to a concentrationof 0.5 mg/ml using 50 ml-volumetric flasks. The solutions wereultrasonicated for 5 min. Thiabendazole, flubendazole, triclabenda-zole and praziquantel were dissolved in dimethyl sulfoxide (DMSO)(Sigma-Aldrich, Buchs; Switzerland) to 10 mg/ml stock solutions.For the calibration line, drug solutions were diluted in ammoniumformate buffer (25 mM, pH 4.0) in a 2-fold serial dilution with con-centrations between 0.31 �g/ml and 10 �g/ml.

2.5.3. Sample solutions and quantification of active ingredientFive tablets, or less if more were not available, were weighed and

pulverised. The tablet powder was dissolved in 0.25% hydrochlo-ric acid in methanol, corresponding to 0.25 mg/ml albendazole ormebendazole using 50 ml-volumetric flasks. The solutions wereultrasonicated for 10 min and filtered through a mesh of 0.45 �m.The samples were diluted in ammonium format buffer (25 mM, pH4.0) to a concentration corresponding to 5 �g/ml and analysed. Thecalculated amount of active ingredient of each sample was com-pared with the nominal amount. We applied an acceptance rangeof 90–110% of active ingredient in the tablets, which was adoptedfrom WHO guidelines (WHO, 2011).

2.5.4. Analytical parametersFor chromatographic measurements, a reversed-phase XB-C18

column (150 × 4.6 mm; 2.6 �m; Phenomenex; Torrance, CA, USA)was used as solid phase. Mobile phase A consisted of ammoniumformate buffer (25 mM, pH 4.0) and mobile phase B of acetonitrile. Agradient from 10% to 100% B and back to 10% B, over 6 min at a flowrate of 1 ml/min was used for drug elution. An injection volume of50 �l was chosen.

Liquid chromatography combined with tandem MS (LC–MS/MS)measurements for praziquantel was performed according to pub-lished protocols (Meister et al., 2016). The mass spectrometricparameters of triclabendazole were optimised by direct infusionof 1 �g/ml drug in methanol into MS/MS.

3. Results

3.1. Human schistosomiasis: perception, health seekingbehaviour and treatment

The total number of randomly selected participants was 401.Out of this number, 63 were diagnosed with a Schistosoma

infection and 50 of them were interviewed. Additionally, sevennon-randomly selected individuals sought care from the studynurse after suspecting that they had schistosomiasis. They testedpositive and also took part in the questionnaire interview.

94 H. Greter et al. / Acta Tropic

Table 1Self-reported symptoms among 57 schistosomiasis patients; overall, and stratifiedby infection with S. haematobium and S. mansoni.

Symptom All schistosomiasispatientsn (%)

Infection withS. haematobiumn (%)

Infection withS. mansonin (%)

Abdominal pain 45 (79) 27 (77) 18 (82)Pain when urinating 29 (51) 18 (51) 11 (51)Headache 20 (35) 10 (29) 10 (45)Blood in urine 15 (26) 11 (31) 4 (18)Joint pain 11 (19) 5 (14) 6 (27)Chest pain 8 (14) 4 (11) 4 (18)Back pain 8 (14) 5 (14) 3 (14)Colored urine 6 (10) 4 (11) 2 (9)Itching 5 (9) 3 (9) 2 (9)Renal pain 4 (7) 1 (3) 3 (14)Constipation 3 (5) 2 (6) 1 (5)

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Weight loss 1 (2) 1 (3) 0Asymptomatic 5 (9) 3 (9) 2 (9)

An infection with S. haematobium was diagnosed in 35 indi-iduals, whereas the remaining 22 individuals were infectedith S. mansoni. No co-infection was observed. Up to six

ymptoms were reported by Schistosoma-positive individu-ls. Abdominal pain (79%) was the predominant symptom,egardless of whether the causative agent was S. haema-obium or S. mansoni. Additionally, patients identified with. haematobium reported pain when urinating (51%) and bloodn urine (31%). Individuals infected with S. mansoni also reportedain when urinating (51%), headache (45%) and joint pain (27%)Table 1). None of the patients reported blood in stool, diarrhoea orloody diarrhoea. Five individuals did not report any kind of symp-oms. Of note, we did not probe for specific symptoms; hence theata reported here refer to spontaneous responses.

Among the 52 schistosomiasis patients who reported one oreveral symptoms, 22 (42%) did not seek treatment. Health cen-res were visited by 17 individuals (32%), with twice as many

ale patients (n = 11; 65%). Doctor choukou were consulted by4 of the patients (26%) with equal numbers of male and femaleatients. Traditional treatment procedures or self-medication wasarely undertaken and exclusively reported from male participantsFig. 2 ).

Medication received at health centres or from doctor choukouas reported as pill or injection (Table 2). A product name or API of

drug was not known by any patient. If asked about the perceivedreatment outcome, a slight improvement for a short 2- to 3-dayeriod was reported, before the symptoms appeared again.

.2. FGDs on animal health: priorities, access to treatment andutcome satisfaction

A total of 17 FGDs were conducted (Table 3). Among the live-tock diseases that were discussed as priorities, fascioliasis wasentioned as highly important by all participating groups of Arab,

ulani and Buduma pastoralists (n = 14). For Gorane pastoralists

able 2ummary of terms used to describe medical treatments and human and animal disease in

English French

Pill Comprimé

Injection Injection

Intestinal worms Vers

Fasciola infection Douve

Haematuria (babesiosis) Infection urinaire (piroplasmose)

Anthrax Charbon

Foot-and-mouth disease Fièvre aphteuse

Lung disease (CBPP) Infection respiratoire (PPCB)

Refers to intestinal parasites in humans; +refers to intestinal parasites in animals.

a 175 (2017) 91–99

(n = 3), bovine babesiosis was of particular importance, which wasreported as haematuria (Table 2). Other diseases put forth as prior-ities were anthrax, foot-and-mouth disease and contagious bovinepleuropneumonia (CBPP), which was reported as lung disease. Asummary of these disease names in all languages used during theFGDs is presented in Table 2. Additionally, the presence of tsetseflies was reported as a livestock health concern (Table 3).

Mobile pastoralists obtained veterinary drugs for use againstfascioliasis from markets, veterinary pharmacies in N’Djamena anddoctor choukou. Those who emphasised fascioliasis as a priorityconsistently named at least one drug product. Satisfaction withfascioliasis treatment outcome was reported as low, particularlyafter administration of drugs purchased from local markets. Othersstated that treatment efficacy was arbitrary; a drug might have apositive effect on animal health, while subsequent treatments withthe same drug showed no effect. It was also stated that drugs fromveterinary pharmacies in N’Djamena might lead to a better healthoutcome than drugs from local markets or doctor choukou (Table 3).However, because travel to the city is time consuming and expen-sive, and prices at veterinary pharmacies are relatively high, thepastoralists continue to use drugs from non-authorised sources.

Besides these reports, mobile pastoralists were concernedabout unsatisfactory treatment outcomes for suspected livestockfascioliasis. In several FGDs, it was elaborated that perceived unsat-isfactory treatment outcomes could be due to the low quality ofdrugs. One group leader brought this concern to the point by stat-ing: «We simply have to believe what the drug sellers tell us and use theproducts they sell us. But we think we get betrayed with drugs of badquality, or even falsified drugs, due to our illiteracy» (male participant,aged 45 years).

3.3. Anthelminthic drug analysis

3.3.1. API content of locally available drugsOverall, 33 products sold as anthelminthic drugs were pur-

chased from different sources (N’Djamena: eight from markets, fourfrom veterinary pharmacies, one from a licensed pharmacy; LakeChad: 11 from markets, six from doctor choukou and three fromhealth centres). At all outlets, drugs were stored at local ambienttemperatures (18–48 ◦C). Upon arrival at the analytical facilitiesin Switzerland, the products were stored at room temperature(22 ◦C). No drugs obtained in the original packaging had passed theexpiry date when purchased. For the benzimidazoles albendazole,mebendazole, flubendazole, thiabendazole and triclabendazole, wedetermined the quantity of API in each sample, and compared itwith the nominal amount (Figs. 3 and 4). The calibration lines werelinear with a goodness of fit (R2) of >0.995.

Among all products, nine were designated for human use(Table 4) and 22 for veterinary use (Tables 5, 6 and 7). For two

samples sold without the original packaging, the target speciescould not be clarified; however, one of them contained meben-dazole at 159% of the labelled amount, while the other containedalbendazole (107 mg) but had no amount labelled (Table 6). All

all languages used during questionnaire interviews and FGDs, and in English.

Chadian Arabic Kanembu Fulbe

Quinin Quinitum QuininIbre Lira BaatelHanish* / Dut+ Guli liu DjildiiDut djite Guli matum BabareOuadja bol – –Abou-tchabaga and Bièdre Bantu ndjulum Da-tewaAblissem Nglam MboruFashfash Gurufu Hendu

H. Greter et al. / Acta Tropica 175 (2017) 91–99 95

Table 3Findings from 17 FGDs on livestock health priorities, treatment seeking and drug sources, fascioliasis treatment and satisfaction with treatment outcome, stratified by ethnicgroups.

Characteristic Ethnic group

Gorane Arab Fulani Buduma

Priority livestock diseases BabesiosisAnthraxFoot-and-mouthdiseaseDiarrhoeaCBPPa

FascioliasisBabesiosisFoot-and-mouth diseaseTsetse flyCBPP

FascioliasisAnthraxBabesiosisFoot-and-mouth diseaseCBPP

FascioliasisCBPPFoot-and-mouth diseaseTsetse flyAnthrax

Treatment source MarketDoctor choukou

Veterinary pharmacy in N’DjamenaMarketDoctor choukou

MarketVeterinary pharmacy in N’DjamenaDoctor choukou

Market

Drugs used to treat fascioliasis n.a. BenzalColours of tabletsb

DistoVermita

BenzalDistoIvomecVermitaVermitol

Colours of tabletsb

Disto

Satisfaction with treatmentoutcome

n.a. Low (for market drugs) Low (for market drugs)ArbitraryBetter (for drugs from veterinary

pharmacy in N’Djamena)

Arbitrary

n.a.: Gorane pastoralists did not prioritise fascioliasis, and hence, these questions were not addressed with these groups.a Contagious bovine pleuropneumonia.b Some pastorlists who did not know a product name reported the colours of tablets used.

Table 4Drugs sold as anthelminthic treatment in humans, purchased in Chad between September 2014 and March 2015.

Sample namea Country of origina Druga Drug detected Nominal drug amount [mg]a Percentage of labelled amount [%]

Zentel South Africa ABZ ABZ 400 150Zenlee India ABZ ABZ 400 93INRESA Albendazole France ABZ ABZ 400 98Vermox Belgium MBZ MBZ 500 152Wormex India MBZ MBZ 500 104Mebendazole n.p. MBZ MBZ 500 117Mebendazole Denmark MBZ MBZ 100 98Diameb India MBZ MBZ 100 147Lokel’s Mebendazole India MBZ MBZ 100 127

ABZ: albendazole; MBZ: mebendazole; n.p.: not provided.a As labelled on original packaging.

Table 5Veterinary use drugs sold as fascioliasis treatment, purchased in Chad between September 2014 and March 2015.

Sample namea Country of origina Druga Drug detected Nominal drug amount [mg]a Percentage of labelled amount [%]

Benzal France ABZ ABZ 2500 129Alben (white) n.p. ABZ ABZ 2500 130Alben (green) n.p. ABZ ABZ 2500 100Albendazole n.p. ABZ ABZ 2500 126LOBS Alben France ABZ ABZ 2500 108Ceva Vermitan Romania ABZ ABZ 2500 119Benzal France ABZ ABZ 2500 130Albendazole n.p. ABZ ABZ 2500 121Benzal France ABZ ABZ 2500 98Benzal France ABZ ABZ 300 124LOBS Alben France ABZ ABZ 300 95Albaneet China ABZ ABZ 250 107NB n.p. ABZ ABZ 250 91Albenor Nigeria ABZ ABZ 250 107Albenor Nigeria ABZ ABZ 150 109

ABZ: albendazole; n.p.: not provided.a As labelled on original packaging.

Table 6Mebendazole or albendazole containing drugs with incomplete information, purchased in Chad between September 2014 and March 2015.

Sample namea Country of origina Druga Drug detected Nominal drug amount [mg]a Detected amount [mg] Percentage of labelled amount [%]

Mebendazoleb n.p. MBZ MBZ 500 794 159n.p.b n.p. n.p. ABZ n.p. 107 n.a.Vermitac n.p. n.p. ABZ n.p. 173 n.a.

ABZ: albendazole; MBZ: mebendazole; n.a.: not applicable; n.p.: not provided.a As labelled on original packaging.b Target species not known.c Veterinary use drug.

96 H. Greter et al. / Acta Tropica 175 (2017) 91–99

F the ss

tzonldlb

ig. 2. Self-reported health seeking behaviour from 52 schistosomiasis patients fromtratified by sex.

ablets for human use contained albendazole (n = 3) or mebenda-ole (n = 6), with the amounts of API ranging between 93% and 152%f the labelled amount (Table 4). Among the 22 samples for veteri-ary use, 15 contained albendazole at levels of 91% to 130% of the

abelled amount (Table 5). For one veterinary use product with noosage labelled, an amount of 173 mg of albendazole was calcu-

ated (Table 6). Five products were sold unpacked without originalox or blister, but with a hand written notation of the product

Fig. 3. Amount of albendazole and mebendazole in the analysed tablets for hum

outh-eastern Lake Chad area, interviewed between September 2013 and May 2014,

name. Tests performed revealed that they did not contain albenda-zole, mebendazole, flubendazole, thiabendazole, triclabendazole orpraziquantel. Among these, the two products sold under the nameDisto were reported to contain bithionol sulfoxide, but we did notperform analysis for this API. Another drug for veterinary use soldas an anthelminthic was reported as an antibacterial tetracycline

(Table 7).

an use from Chad, purchased between September 2014 and March 2015.

H. Greter et al. / Acta Tropica 175 (2017) 91–99 97

Fig. 4. Amount of albendazole in the analysed tablets for veterinary use from Chad, purchased between September 2014 and March 2015.

Table 7Veterinary drugs for the treatment of fascioliasis in livestock with incomplete information whose API could not be identified. Drugs were purchased in Chad betweenSeptember 2014 and March 2015.

Sample (name as reported) Drug labelled Drug information from veterinary pharmacists ABZ, MBZ, FBZ, TBZ, TCZ, PZQ detected

Disto No Bithionol sufloxide NoDisto No Bithionol sulfoxide NoBalmizole 3 No Not known NoVermizol No Not known NoVolimizol No Not known No

ine HC

A thiab

4

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PSE Terravet No Oxytetracycl

BZ: albendazole; FBZ: flubendazone; MBZ: mebendazole; PZQ: praziquantel; TBZ:

. Discussion

Among mobile pastoralists living in the Lake Chad area, wessessed access to, and common practice of, drugs for the treatmentf human and animal trematode infections in a setting with poorlyeveloped human and veterinary health systems. Awareness of

ivestock fascioliasis was high, confirming findings from earliertudies at Lake Chad (Jean-Richard et al., 2014), which underscoreshe importance of the disease. Although the disease is not diag-osed by a veterinarian, earlier studies have shown that empiriciagnosis and traditional knowledge of symptoms of fascioliasis

s quite accurate in Fulani pastoralists in the area (Schillhorn vaneen, 1997). Indeed, mobile pastoralists frequently undertake fas-ioliasis treatment with locally available products, showing thathe willingness to pay for treatment is generally high. In contrasto other livestock diseases, no traditional treatment is practicedor fascioliasis. Self-mediated therapy with drugs obtained from

arkets, doctor choukou and veterinary pharmacies is the commonractice to treat livestock with suspected fascioliasis. Most of theserugs tested contained albendazole. Albendazole is still used as aukicide in livestock in resource-constrained settings, since it is

nexpensive and safe. Its efficacy is, however, limited to adult Fasci-la flukes and therewith generally low (Buchanan et al., 2003). Twoamples were reported to contain bithionol sulfoxide, an old treat-ent rarely used today as a flukicide (Mehlhorn, 2008). At present,

he most efficacious drug available to treat fascioliasis is triclaben-azole, which has a high margin of safety and, additionally, killsoung developing stages of Fasciola (Keiser et al., 2005). Triclaben-azole was not detected among the samples purchased, neither at

ocal markets around Lake Chad nor in N’Djamena. To our knowl-dge, triclabendazole is not yet licensed in Chad. Additionally, aboutalf of the drugs tested were of substandard quality due to over

oncentration of API, exceeding the labelled amount of albenda-ole by more than the accepted threshold of 110% (Caudron et al.,008). Of note, we present a snap-shot of anthelminthic drug sam-

l No

endazole; TCZ: triclabendazole.

ples obtained from the Lake Chad area, and a larger study is requiredto confirm our results. Also, it is worth stating that in the presentstudy, we did not examine other parameters for drug quality, suchas tablet dissolution or friability. We exclusively focused on the typeand amount of API as broad quality proxies. A recent comprehen-sive study from Ethiopia investigated the quality of anthelminthicdrugs, including all pharmaceutical parameters and found about 8%of the tested samples of albendazole and over 40% of mebendazoleto be overdosed (Suleman et al., 2014).

Among the human schistosomiasis cases, about 60% reportedseeking treatment, in equal parts at governmental health cen-tres and with doctor choukou. Male patients had better access tohealth centres than their female counterparts. This finding reflectsthe well-known custom that among the ethnic groups of mobilepastoralists in the study area, women can only attend a healthcentre with the permission of their father, husband or brother(Hampshire, 2002). Regarding human schistosomiasis and humanhelminth infections in general, knowledge remained non-specific,and no distinction could be made between different parasitic dis-eases. None of the patients were aware of a drug name or APIto treat parasitic worm diseases. All drugs purchased and testedin our study to treat human helminthiases contained exclusivelyalbendazole or mebendazole. These were available and accessibleat health centres, in markets and from doctor choukou. The lackof laboratory diagnostics for helminth infections at health centres,thus dictating exclusively empiric diagnoses, may explain the selec-tion of this therapy. Still, patients reported a slight improvement for2–3 days after treatment, before symptoms reappeared. This mayalso hold true for antibiotic treatment administered by health cen-tre staff or doctor choukou, who may interpret the most frequentlystated symptoms of schistosomiasis patients as bacterial urinarytract infections.

Similarly to the veterinary drugs, half of the tested drugs forhuman use were found to contain an over concentration of alben-dazole or mebendazole, as observed earlier in Chad and elsewhere

9 Tropic

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n resource-constrained settings (Caudron et al., 2008). Neverthe-ess, all products contained more than 90% of the labelled drug.hese results do not support the pastoralists’ hypothesis of prod-cts circulating with insufficient amount or even absence of API.onetheless, albendazole or mebendazole are not effective against. haematobium, S. mansoni and S. bovis, and have very limitedctivity against F. gigantica. Praziquantel, the drug of choice toreat schistosomiasis, was not identified among the samples tested.lthough it is available from licensed pharmacies in N’Djamena, ourndings indicate that praziquantel is not available at rural healthentres in the study area and on the informal drug market.

The present study was restricted to the south-eastern Lake Chadrea and the mobile pastoralist population encountered there;ence, the picture drawn represents a narrow insight to the topicddressed. A study including the sedentary population but also theealth sector in the study area, together with a nationwide study onnthelminthic drug quality and availability, should be performed toave a deeper understanding of the situation.

We conclude that with regard to livestock fascioliasis, aware-ess, willingness to treat and pay for treatment was high. Accesso human and veterinary anthelminthic treatment exists, predom-nantly through the informal sector. The tests performed on theample of drugs purchased from different outlets revealed thatome products did not meet minimal quality standards. Yet, theeported low treatment success is unlikely due to the low qualityf drugs, but rather caused by the lack of availability of reliableiagnostic tools and efficacious drugs, i.e. praziquantel and tri-labendazole. Regarding livestock health, the non-availability ofriclabendazole for fascioliasis treatment leads to an additionalconomical loss for the mobile pastoralists, since financial meansre spent on sub-standard treatment. Introducing efficacious treat-ent against livestock fascioliasis will thus not only impact on

nimal health, but also result in economic benefits by improvingroductivity and reducing treatment costs.

Regarding human health, more than half of the interviewedndividuals infected with schistosomiasis sought treatment. Rapidiagnostic tests (RDTs) for the detection of S. mansoni are now avail-ble, which might allow for improved management of the diseaseColley et al., 2013). Reagent strip testing for microhaematuria asn indicator of urogenital schistosomiasis is widely used, since its easy to perform. Although its sensitivity is only about 75% andts use as sole diagnostic tool is currently under discussion (Krautht al., 2015), it has the potential to distinguish an active S. haema-obium infection from a bacterial urinary tract infection, and hencean guide health staff to the selection of the appropriate treatment.romoting these diagnostic tools in health centres and introduc-ng praziquantel, accompanied by awareness campaigns amonghe general public and training for health personnel might be theay forward to reduce the burden of schistosomiasis in Chad and

lsewhere.

unding

This study received financial support by the Swiss National Sci-nce Foundation (Bern, Switzerland; grant no. 320030 141246),he Rudolf Geigy Foundation (Basel, Switzerland) and the Freiekademische Gesellschaft (Basel, Switzerland). JK is grateful to theuropean Research Council (ERC-2013-CoG 614739-A HERO) fornancial support.

cknowledgements

We thank all study participants and the Chadian team for theirxcellent work in the field laboratory under challenging environ-ental conditions. Special thanks go to Mrs. Hadje Falmata, Mr. Ali

a 175 (2017) 91–99

A. Abakar and Mr. Moussa Issa for their outstanding skills in facili-tating communication across cultures and different languages. Wethank Daniel Ehrsam for his help during the drug analysis and LisaCrump for useful comments on an earlier version of this manuscript.

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