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[08/04/2005]
 Central African Republic
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Author :

Dr Francis LOUIS, Yaoundé, Cameroon 

 

Aknowledments:

Pr Jean DELMONT, Marseille, France 

Dr Justin N’DOYO, Bangui, Central African Republic

Mme Dominique LOUIS-LUTINIER, Yaoundé, Cameroon.     

Mme Odile SOSSAT, I.M.T.S.S.A. Le Pharo, Marseille, France     




> General information on the country | > Epidemiology of malaria | > The parasites and chemo-resistance | > The vectors and anti-vectoral action | > The treatment of malaria | > Advice to travelers | > References

 General information on the country

surface area: 623,000 km2
population: 3,282,480 inhabitants 
official language: French
currency: franc CFA (1 Euro = 656 FCFA)
neighboring countries: Cameroon, Chad, Sudan, Democratic Republic of the Congo, Republic of the Congo. 
capital: Bangui
main towns: Bangui, Bouar, Berbérati, Bossangoa, Bangassou.

The Central AFrican Republic:

The Central African Republic, formerly Oubangui-Chari, is a totally landlocked country in the heart of central Africa. 
Three main climatic regimes are to be found here (17) :
- the southern part of the country (Bangui, Berbérati, Bangassou) is subjected to a Guinean forest or equatorial climate, favorable to the development of endemic malaria with permanent transmission,
- the central part (Bouar, Bossangoa, Bambari) is subjected to a Sudanese-Guinean type climate favorable to the development of endemic malaria with permanent transmission and seasonal outbreaks,
- the northern part (Birao) is subjected to a Sudanese-Sahelian type climate     favorable to the development of endemic malaria with episodic transmission
 Epidemiology of malaria
Malaria is endemic throughout the country.
A study conducted by Brumpt et al. in 1971 in a rural setting in the north of the country shows a rate of 72% of hematozoa carriers. The population suffers little from malaria, acquiring immunity from it at a very early stage (02). 
For Testa et al. who, in 1987 studied a group of 500 women at Bangui, the plasmodial index was 35.6% among pregnant women and 28.6 % among non-pregnant women (03).
In 1988, the plasmodial index observed was 40.4 % at Bangui, 31.7 % at Bambari, 36.2 % at Berbérati, 67.8 % at Bossangoa, 55.1 % at Bangassou and 62.9 % at Bouar (09).
For Monges et al., the plasmodial index among 342 children of less than 15 years of age at Bangui was 16 % (07).
 The parasites and chemo-resistance

Plasmodium falciparumis the parasitic species the most widely represented in the Central African Republic: 96 % according to Brumpt et al. (02). 
With a frequency of 16.7%, Plasmodium malariae is to be found very far behind (02). 

Resistance to chloroquine :

In 1987, Pierce et al. signaled a failure of chloroquine prophylaxis; tested in vitro, the strain was chloroquine-resistant (04). But the same year, Jean Delmont et al. showed that resistance of Plasmodium falciparumto chloroquine went back to 1983 (05). 
The RIII type resistances remain quite exceptional (05,07,19). In 1992, Jean Delmont et al. insisted on the continuing efficacy of chloroquine at a dosage of 25 mg/kg spread over 3 days (27), but in 2003, I. Bergeri et al. indicated that with this dosage, the precocious therapeutic failures varied from 9% to 40 % and the late failures from 4% to 9%, depending on the region: hence a total of 16% failures were noticed at Berbérati, 18 % at Bangassou and Bambari, 19 % at Bossangoa and 48 % at Bangui (37). 

Table 1 : in vivo resistance to chloroquine in the Central African Republic:  

Year   Chloroquine Number studied Results Réf 
1984 10 mg/kg single dose 31 schoolchildren 2 RI/RII 05, 08 
1984 25 mg/kg over 3 days 14 febrile children no failure 05, 08 
1985 10 mg/kg single dose 29 schoolchildren 1 RI/RII 05, 08 
1985 25 mg/kg over 3 days 43 febrile children 1 RII 05, 08 
1986 10 mg/kg single dose 25 febrile children 6 RI/RII 05, 08 
1986 25 mg/kg over 3 days 34 febrile children no failure 05, 08 
1986 10 mg/kg single dose 80 febrile children 6 failures 10 
1987 25 mg/kg over 3 days 23 febrile children 2 RII 07 
1989 25 mg/kg over 3 days 204 schoolchildren around 10% RI/RII 19 
2003 25 mg/kg over 3 days 268 febrile children therapeutic failures 37 
16% à 48% 




In vitro, no meaningful study has been published.

Resistance to other antimalarial drugs:

It has been very little studied. 

- Amodiaquine: no failure was highlighted in 1986 in a group of 21 febrile children treated with 25 mg/kg of amodiaquine over 3 days (05). 

- Quinine: one case of prophylaxis failure and one treatment by the chloroquine-sulfadixine-pyrimethamine combination was successfully treated by quinine in1988 (11).
- Mefloquine: no study published.
- Halofantrine: in 1991, H. Darie et al. mention the emergence of resistance to halofantrine (20). But in 1992, D. Baudon et al. demonstrate the efficacy of a radical cure by halofantrine on return from Central Africa (24).
- Sulfadoxine-pyrimethamine combination: in 1988, L. Bélec et al. reported the case of a subject under chemoprophylaxis combining chloroquine and the combination sulfadoxine-pyriméthamine, who developed malaria, which was unfortunately treated initially by the same combination of antimalarial drugs. Faced with an aggravation of his state, he was finally successfully treated with quinine (11). 
- Other antimalarial drugs: no publication.


Recommendations of the National Anti Malaria Program :

Since May 2005, the NAMP recommends coartem as first line and second line treatment.

 The vectors and anti-vectoral action

No publication on the subject has been found.

 The treatment of malaria

In 1989, Jean Delmont et al. recommended chloroquine at a dose of 25 mg/kg spread over 3 days (19).

No other study on the subject has been published since.

 Advice to travelers

In its 2005 edition of sanitary recommendations for travelers, the Institut français de veille sanitaire classifies the Republic of Central Africa in Group 3 of the « zones of highly prevalent chloroquine resistance, or multi-resistance » (38), which would appear surprising given the little information available on chloroquine resistance in the country. This means that the chemoprophylaxis recommended is Mefloquine, the Atovaquone-Proguanil combination or Doxycycline. 

The French military who have spent a long time in Central Africa, paid particular attention to the study of the question of the protection of troops stationed in the country :
- in 1989, F. Lallemand et al. studied a group of 141 military personnel who were stationed for 4 months in the RCA and were under a chloroquine prophylaxis (100 mg/day). 41 required hospitalization for malaria (29%)(15).
- in 1990, the French military stationed in the RCA were given the combination chloroquine-proguanil . 
- in 1991, O. Dupuy et al. studied a group of 131 military personnel under a  chloroquine-proguanil combination prophylaxis: with an observance of 100 %, 3 military developed malaria (2.3 %)(28).
- in 1993, D. Garin et al. showed that the risk of contracting malaria while under   chloroquine is 0.0012/day/man and 0.0003/day/man while under the combination chloroquine-proguanil (29).
- in 1999, 13 cases of malaria were diagnosed in 270 military under the chloroquine-proguanil combination (4.8 %) and a single case in 171 military under doxycycline (0.6 %)(33).  

Among the measures of protection the simple and efficacious measures for individual protection against the bites of Anopheles mosquitos should not be forgotten: repellents and bed nets impregnated with a residual insecticide. 

 References

01 - Chastel C, Thomas J - Elliptocytose constitutionnelle et paludisme. Bull. Soc. Path. Ex. 1968; 61: 605-13. 

02 - Brumpt LC, Ho Thi Sang, Jaeger G - Quelques réflexions à propos du parasitisme sanguine et intestinal dans deux villages d’Afrique Centrale. Bull. Soc. Path. Ex. 1972; 65: 263-70. 

03 - Testa J, Baquillon G, Delmont J, Kamata G, Ngama G - Grossesse et indices parasitémiques à Plasmodium falciparum  (résultats d’une étude à Bangui, R.C.A.). Méd. Trop. 1987; 47: 339-43. 

04 - Pierce PF, Milhous WK, Campbell CC - Clinical and laboratory characterization of a chloroquine-resistant Plasmodium falciparum strain acquired in the Central African Republic. Am. J. Trop. Med. Hyg. 1987; 36:1-2. 

05 - Delmont J, Testa J, Monges P, Limbassa J, Georges AJ, Faugère B - Etat de la chimiorésistance de Plasmodium falciparum en République Centrafricaine. Résultats d’enquêtes menées de 1984 à 1986. Bull. Soc. Path. Ex. 1987; 80: 434-42. 

06 - Desfontaine M, Cathebras P, Delmont J, Testa J, Bechen R, Somse P, Roungou JB - Surveillance de l’extension de la chloroquino-résistance de Plasmodium falciparum en Centrafrique. Résultats de 25 tests in vivo réalisés à Bangassou (région sanitaire 5) - juillet 1987. Bull. liais. doc. OCEAC 1987; 82: 45-7.

07 - Monges P, Josse R, Merlin M, Testa J, Limbassa J, Gouaut P, Quilici M, Ngama G, Delmont J - Evaluation des indices paludométriques à Bangui (octobre 1985). Méd. Afr. Noire 1987 ; 34: 3.

08 – Delmont J, Testa J, Monges P, Ngama G, Desfontaine M, Ravollet JC, Limbassa J – Evaluation de la chimiosensibilité de Plasmodium falciparum aux amino-4-quinoléïnes dans trois villes de la République Centrafricaine. Résultats de 254 tests in vivo réalisés de 1984 à 1986. Bull. Liais. Doc. OCEAC 1987, 125-128.

09 – Delmont J, Testa J, Sarda J, Roungou JB, Desfontaine M – Situation de la chimiorésistance de Plasmodium falciparum aux amino-4-quinoléïnes en République Centrafricaine (1983-1988). Bull. Liais. Doc. OCEAC 1988, 43-44.

10 – Debat-Zoguereh D, Delmont J, Testa J, N’Gama G – Etude in vivo de la chimiorésistance de Plasmodium falciparum aux amino-4-quinoléïnes chez des enfants Centrafricains. Med. Afr. Noire 1988, 35 : 101-104.

11 - Belec L, Delmont J, Vesters I, Testa J, Christian KS, Georges AJ - Emergence de paludisme à Plasmodium falciparum multirésistant en République Centrafricaine. Presse Méd. 1988; 17: 2090-1.

12 - Miller KD, Campbell GH, Nutman TB, Mulligan M, Currie B, Procell PM, Roberts
JM - Early acquisition of antibody to Plasmodium falciparum sporozoites in non-immune temporary residents of Africa. J. Infect. Dis. 1988; 158: 868-71. 

13 - Chagnon A, Talard P, De Jaureguiberry JP, Mafart B, Pierre C, Carli P, Dussarat G - Splénomégalie malarique hyperréactive chez un européen revenant d’Afrique Centrale. Presse Méd. 1989; 18: 938. 

14 - Belec L, Bourée P, Testa J, Delmont J, Quenum B, Georges AJ - Extension of multiple drug resistant Plasmodium falciparum malaria in Africa: report of  a Central African case. Biomed. Pharmacother. 1989; 43: 699-702. 

15 - Lallemand F, Testa J, Monges, Bentresque P, Hervé V, Georges AJ, Delmont J -  Chloroquinorésistance du Plasmodium falciparum en Centrafrique. Incidence et distribution géographique. Médecine et Armées 1989 ; 17: 479-82.

16 – Delmont J, Siopathis RM, Testa J, Roungou JB, Monges P, Yaya FM, Ngama G, Kanda P, Ndonazi B, Madji N, Bendje N – Evaluation de la chimiorésistance de Plasmodium falciparum à la chloroquine chez des enfants Centrafricains : bilan de cinq années (1984-1988) d’études par tests in vitro. Méd. Afr. Noire 1989; 36: 499-500.

17 – Desfontaine M – Chimiorésistance de Plasmodium falciparum aux amino-4-quinoléïnes en Afrique Centrale. Nouvelles perspectives de lutte. Mémoire de spécialité de recherches du SSA, 1990, 64 pages.

18 - Testa J, Awodabon J, Lagarde N, Olivier T, Delmont J - Indices plasmodiques et placentopathies palustres chez 229 parturientes centrafricaines. Med. Trop. 1990; 50: 85-90.

19 - Delmont J, Bouquety JC, Testa J, Olivier T, Roungou JB, Georges AJ, Siopathis RM - Chimiorésistance du paludisme et attitudes thérapeutiques nouvelles en République Centrafricaine. Méd. Afr. Noire 1990; 37: 380-1.

20 - Darie H, Reyle Y, Hovette P, Touze JE -  Aspects actuels du paludisme chez l’expatrié en république de Centrafrique. Med Trop. 1991; 51: 441-4. 

21 - Testa J, Awodabon J, Lagarde N, Olivier T, Delmont J - Intérêt de l’apposition placentaire comme marqueur épidémiologique du paludisme. Bull. Soc. Path. Ex. 1991; 84: 473-9. 

22 - Olivier T, Paufique-Olivier M, Delmont J, Sirimbo M, Vohito JA, Testa J, Tamalet C, Siopathis RM, Pene P - Virus de l’immunodéficience humaine (VIH) et paludisme chez des donneurs de sang en République Centrafricaine. Méd. Afr. Noire 1991; 38: 175-9.

23 - Brinkmann U, Brinkmann A - Malaria and health in Africa : the present situation and epidemiological trends. Trop. Med. Parasitol. 1991; 42 : 204-213.

24 - Baudon D, Bernard J, Mouliat-Pelat JP, Martet G, Sarrouy J, Touze JE, Spiegel A, Lantrade P, Picq JJ - Efficacité de la cure radicale par halofantrine sur la prévention du paludisme d’importation à Plasmodium falciparum. Ann. Soc. belge Méd. Trop. 1992; 72: 263-70. 

25 - Vachon F, Fajac I, Gachot B, Coulaud JP, Charmot G - Halofantrine and acute intravascular haemolysis. Lancet 1992; 340: 909-10. 

26 - Lanckriet Ch, Bureau JJ, Capdevielle H, Gody JC, Olivier T, Siopathis RM -  Morbidité et mortalité dans le service de pédiatrie de Bangui (Centrafrique) au cours de l’année 1990 - implications en matière de Santé Publique. Ann. Pédiatr.(Paris) 1992; 39:125-30. 

27 - Delmont J, Testa J, Courtois P, Capdevielle H, Le Tien C, Roungou JB - Persistence of low levels of Plasmodium falciparum resistance to chloroquine in
the autochtonous population of the Central African Republic. J. Hyg. Epidemiol. Microbiol. Immunol. 1992; 36: 362-7.

28 - Dupuy O, Garin D, Robet Y, Dusseau JY, Lamarque D - Etude de la tolérance de l’association chloroquine - proguanil dans la prophylaxie anti-palustre de 131 militaires ayant séjourné en RCA. Méd. Mal. Infect. 1992 ; spécial : 621-3.
 
29 - Garin D, Lamarque D, Ringwald P, Dupuy O, Chaulet JF, Chapalain JC, Fléchaire A - Efficacy of chloroquine-proguanil chemoprophylaxis against malaria in the Central African Republic. Trans. R. Soc. Trop. Med. Hyg. 1993; 87: 304-5. 

30 - Coué JC, Martet G, Vigier JP, Mathiot C, Peyron F - Le diagnostic des accès palustres en Afrique par le test Parasight™F. Med. Trop. 1995; 55: 333-5. 

31 - Weaver M, Ndamobissi R, Kornfield R, Blewane C, Sathe A, Chapko M, Bendje N, Nguembi E, Senwara-Defiobona J - Willingness to pay for child survival: results of a national survey in Central African Republic. Soc. Sci. Med.1996; 43: 985-98. 

32 - Baron E - Incidence du paludisme dans les armées françaises en République Centrafricaine de 1988 à 1993. Med. Trop. 1996; 56:100. 

33 - Baudon D, Martet G, Pascal B, Bernard J, Keundjian A, Laroche R - Efficacy of daily antimalarial chemoprophylaxis in tropical Africa using either doxycycline or chloroquine-proguanil; a study conducted in 1996 in the French Army. Trans. R. Soc. Trop. Med. Hyg. 1999; 93: 302-3. 

34 - Destro-Bisol G, Vienna A, Battaggia C, Paoli G, Spedini G - Testing a biochemical model of human genetic resistance to falciparum malaria by the analysis of variation at protein and microsatellite loci. Human  Biol. 1999; 71: 315-32.

35 - Rowe AK, Hamel MJ, Flanders WD, Doutizanga R, Ndoyo J, Deming MS - Predictors of correct treatment of children with fever seen at outpatient health facilities in the Central African Republic. Am.J. Epidemiol. 2000;151:1029-35. 

36 - Bobossi-Serengbe G, Diemer CH, Mbongo-Zindamoyen AN, Vohito MD, Moyen G, Siopathis RM - Les fièvres prolongées de l’enfant : expérience du service pédiatrique du C.N.H.U de Bangui (Centrafrique). Méd. Afr. Noire  2002 ; 49: 344-50.

37 - Bergeri I, Débat-Zoguéreh D, Madji N, Barrau K, Delmont J, Namsenmo A, Ndoyo J - Evaluation in vivo de l’efficacité thérapeutique de la chloroquine pour le traitement du paludisme dû à Plasmodium falciparum non compliqué en Centrafrique en 1997 et 1998] Bull. Soc. Pathol. Exot. 2003; 96: 29-34. 

38 – Institut de veille sanitaire – Recommandations sanitaires pour les voyageurs 2005. Bull. Epidemiol. Hebd. n° 24-25 du 14 juin 2005 : p.117-128.
 

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