• Area: 801,590 km2
• Population: 19,686,500 inhabitants (estimate from July 2006)
• Official language: Portuguese
• Currency: Metical, divided into 100 centavos
• Border countries: Malawi, South Africa, Swaziland, Tanzania, Zambia, Zimbabwe 
• Capital: Maputo (3-6 million inhabitants)   

The country is divided into three zones and comprises 11 provinces (Fig. 1):
- in the north: Niassa (administrative center: Lichinga), Cabo-Delgado (administrative center: Pemba) and Nampula (administrative center: Nampula);
- in the center: Zambézia (administrative center: Quelimane), Tete (administrative center: Tete), Manica (administrative center: Chimoio) and Sofala (administrative center: Beira);
- in the south: Inhambane (administrative center: Inhambane), Gaza (administrative center: Xai-Xai), Maputo province and Maputo city.

Mozambique is composed of coastal lowlands, where the population is concentrated, at an altitude below 200 meters (44% of the country), the planalto, with an altitude between 200 meters and 1,000 meters (43% of the country) and lastly the planalto grand, with peaks from 1,000 meters to 1,500 meters (13%).
The climate is tropical, characterized by temperatures decreasing from the north to the south and in accordance with the altitude. The most rainfall is recorded in the center of the country, where more than 1,300 mm of rain falls from November to June. The climate is dry from July through October. 
The coast of Mozambique is occasionally struck by devastating tropical cyclones. In April 2000, Cyclone Eline ravaged the entire southern part of the country, causing catastrophic flooding. 
The country’s predominant vegetation is savanna woodland, cut by gallery forests. At higher altitude, this is replaced by a steppe.

No recent study has been conducted on malaria epidemiology in Mozambique. In 1952 and 1956, Soeiro established an initial panorama of malaria in Mozambique (01, 02). In 1982, Onori concluded that all of the provinces in Mozambique are extremely endemic, with the exception of Manica, which is meso-endemic, and Maputo, which is hypo-endemic (Table I) (72).

Table I - Prevalence (%) of malaria in Mozambique, by province and by age group
(according to Onori, 1982, cited by Mouchet et al., 2004)

Over the past 30 years, information on Mozambique has been limited to the southern provinces of Maputo and Gaza.
Malaria is the cause of 2% to 5% of hospitalizations (01, 02) and 36% of pediatric fevers seen in hospitals (50).
A study on the incidence of clinical malaria in children in rural areas, conducted from 1996 to 1999, showed that this incidence was practically nonexistent in children under the age of two months and that it was 0.65 to 0.74 episodes per 100 persons per week, with, however, very large geographic variations, with a higher incidence in children living near rivers or in swampy areas (49).
In Maputa, Osman et al. noted a frequency of low birth weight of 16.2%, premature births of 15.4%, natimortality of 4% and perinatal death of 4.7% (44).
Despite inhabitants’ strong level of immunity, floods, with their trail of displaced populations, could lead to malaria epidemics (39, 47). This led Da Silva et al. to propose measures to strengthen the prediction of epidemics and their management: 60% of epidemics must be detected within two weeks from the time they begin and 60% of epidemics must be controlled within two weeks following their detection (61).

Resistance to chloroquine

In vivo:
In 1971, chloroquine used intramuscularly in treating simple malaria remained just as effective (03).
The first case of resistance to chloroquine was described in 1975 in South Africa: it involved a 24-year-old woman from southern Mozambique, presenting with malaria resistant to a standard treatment with chloroquine and yielding to quinine by parenteral route (05).
Eight new cases were published in 1985 (07), followed by two new cases in 1986 (08, 09).
In 1988, Schapira and Da Costa published a study conducted in 1985 and 1986 on children in Maputo and Xai-Xai, showing the extreme inefficacy of chloroquine as a prophylaxis, compared with a placebo (10). 
Also in 1988, Schapira and Schwalbach showed a 94% resistance rate to chloroquine at a dosage of 25 mg/kg for three days (12).
In 2004, the therapeutic efficacy of chloroquine was 47.1% (56).
In vitro: 
In 1988, five of the six malaria strains tested were resistant to chloroquine (12).
In 1991, the in vitro resistance rate to chloroquine was 100%, according to Freese et al., but only eight malaria strains were tested (14).

Resistance to other antimalarial drugs

1. Amodiaquine:
The first case of resistance to amodiaquine was demonstrated in 1985 in Mozambique, for a malaria strain that was also resistant to chloroquine (07).
In 1988, Schapira and Schwalbach noted a 76% resistance rate to amodiaquine at a dosage of 25 mg/kg for three days (12).
In 2004, in vivo, amodiaquine maintained a therapeutic efficacy of 91.6% when used alone, and of 100% when used in combination with sulfadoxine-pyrimethamine or artesunate (56).

2. Quinine:
In 1991, Simao et al. showed the efficacy of quinine intramuscularly (IM) in the treatment of malaria in children (15).
In 1993, quinine given intramuscularly or intravenously remained just as effective in the treatment of severe malaria (table II) (19).
In 2004 in Rome, Palmieri et al. reported a first case of quinine-resistant malaria in a patient who had returned from a trip to the province of Maputo (59).

3. Mefloquine:
Mefloquine was used primarily as a prophylaxis for malaria by Italian troops. From July 1993 through July 1994, 4,000 soldiers stayed in Mozambique, taking mefloquine prophylaxis: only four cases of malaria were recorded (28).
In 1995, Matteelli et al. reported an additional case of prophylaxis failure in an Italian soldier (29), while Cali, and then Peragallo et al. insisted on the very good efficacy of mefloquine as a prophylaxis (30. 31, 37).

4. Halofantrine:
No publication on the subject.

5. The sulfadoxine-pyrimethamine combination:
In 1971, the sulfadoxine-pyrimethamine combination orally was effective in the treatment of 65 patients (03). It was also effective in the monthly suppressive treatment of malaria (03).
In 1986, the first case of resistance to the sulfadoxine-pyrimethamine combination was published, but there was a doubt about the origin of the patient, who had been to Mozambique and Malawi (09). This patient was also resistant to chloroquine.
In 1988, Schapira and Schwalbach noted a 16% resistance rate to the sulfadoxine-pyrimethamine combination, but none to the sulfadoxine-pyrimethamine-amodiaquine combination (12). In the treatment of chloroquine-resistant malaria, the sulfadoxine-pyrimethamine combination alone provides 86% of recoveries and the sulfadoxine-pyrimethamine-amodiaquine combination provides 90% (13).
In 1991, Simao et al. reported seven cases of RII/RIII resistance in 48 children (14.6%) treated with the sulfadoxine-pyrimethamine combination intramuscularly (15).
In 2004, in a study of the sulfadoxine-pyrimethamine combination vs. placebo of 200 pregnant women, Challis et al. demonstrated that the sulfadoxine-pyrimethamine combination remains very effective in the prevention of pregnancy malaria (54). Abacassamo et al. showed that the sulfadoxine-pyrimethamine combination alone was still 82.7% effective in the treatment of malaria in children. When combined with artesunate or amodiaquine, this efficacy was 100% (56).
In 2006, Macete et al. recommended that the sulfadoxine-pyrimethamine combination be administered orally at the third, fourth and ninth months, at the same time as routine regulatory vaccines. In their study, there were no side effects and the incidence of malaria dropped 22.2% and hospitalizations decreased 19% during the first year of life (66).

6. The dapsone-pyrimethamine combination:
The dapsone-pyrimethamine combination was certainly the combination most used and studied in Mozambique.
By 1971, Wolfensberger showed its efficacy (03), which Botelho confirmed in 1973 (04).
However, in 1991, Freese et al. showed in vitro the total inefficacy of pyrimethamine used alone (14).
In 1992, Pividal et al. demonstrated the efficacy of the dapsone-pyrimethamine combination vs. placebo as a prophylaxis for malaria in schoolchildren: in the placebo group, 28 cases of malaria were recorded and none were recorded in the dapsone-pyrimethamine combination group (18).
In a study of 5,744 people in 1995, Dgedge et al. showed that with the dapsone-pyrimethamine combination taken on a weekly basis, the incidence of malaria was 54.7/1,000/6 months against 119.7/1,000/6 months in the control group. In the group taking the dapsone-pyrimethamine combination, malaria accounted for 29.5% of all diseases diagnosed, against 39.5% in the control group (24).

7. Artemisinine derivatives:
It would appear that very few studies have been published on the subject. We have only found the publication of Abacassamo et al. which showed that artesunate, when combined with amodiaquine or the sulfadoxine-pyrimethamine combination, has 100% efficacy in the treatment of simple malaria in children. Artesunate alone was not evaluated in this study (56).

The vectors :
During the 1940’s and 1950’s, Soeiro prepared an inventory of the anopheles found in Mozambique. It was then that he recorded the presence of Anopheles cinereus, An. coustani, An. coustani var. tenebrosus, An. funestus, An. gambiae, An. maculipalpis, An. marshalli, An. marshalli var. mounsihoi, An. pharoensis, An. rivulorum, An. rufipes, An. squamosus and An. squamosus var. cydippis (01).
Mouchet et al., prepared a simple inventory that only includes those anopheles that are with medical interest: anopheles from the gambiae group (An. gambiae, An. arabiensis, An. merus and An. quadriannulatus), An. funestus, An. nili and An. pharoensis (72).
Cuamba and Crook studied the An. arabiensis in Maputo from 1989 to 1991. They showed that its frequency was low during the dry season (July – September) and that frequency peaks out of doors occurred between 21:00 and 22:00 hours and between 24:00 and 01:00 hours. Indoors, the frequency peak occurs between 23:00 hours and midnight (23).
Thompson et al., studied the spatial distribution of malaria. They showed that, depending on the distance of the beds, the number of infested bites (ib) virtually varied from 0 to10 ib/man/year and the prevalence of malaria from 5.4 % to 59 % (32). 
In a study undertaken from 1994 to 1996 in the suburbs of Maputo, Mendis et al., collected 5 893 anopheles using human lures. These anopheles included An. funestus (46 %), and An. coustani (12 %) (38).
In a similar study from October 1997 to September 1998, Aranda et al., collected 1 251 anopheles that included An. funestus (72.3 %), An. terebrosus (13.3 %) and An. gambiae s.l. (2.3 %). In this gambiae group, An. arabiensis accounted for 96.6 % of the species and An. merus for 3.4 %; 12.1 % of the anopheles could not be identified (63).

The fight against vectors
In 1995, Martinenko et al., showed that when cyfluthrine was sprayed inside dwellings, it remained effective for 12 to 13 weeks on walls and for 28 weeks on woodwork. This effectiveness period is far shorter than the malaria transmission period and, accordingly, 2 to 3 applications per annum are required for this method to be totally effective (25).
Crook & Baptista demonstrated the effectiveness of curtains impregnated with permethrine at the rate of 0.5 g permethrine/m2 (27).
In 2000, Hargreaves et al., pointed out the resistance of An. funestus to pyrethrinoids (42). Brooke et al., confirmed this in 2001 (45).
In 2002, Durrheim and Govere showed that applying a repellent containing 15 % of DEET to feet and ankles reduced the number of An. arabiensis bites by 69% (47).
In 2004, Conteh et al., estimated the cost of protection per person protected as part of the fight against vectors by spraying the inside of dwellings with a lasting insecticide at 3.48 dollars US in a rural environment and at 2.16 dollars US in a peripheral urban environment (53). 
In 2005, Hunt demonstrated by means of experiments that the An. funestus resistance to pyrethrinoids increased from generation to generation (65).
In a study carried out from 2000 to 2002, Casimiro et al., Showed that the An. funestus remains sensitive to DDT and to malathion, but that it was extremely resistant to pyrethrinoids in Maputo. Elsewhere it continues to be sensitive to pyrethrinoids. An. arabiensis is also sensitive to DDT and to malathion. In Maputo, it withstands low levels of pyrethrinoids and remains sensitive in the other provinces (67, 68).

Recommendation for travellers

Little data is available on Plasmodium falciparum chemoresistance. Available data seems to indicate significant resistance to chloroquine and to the sulfadoxine-pyrimethamine combination.
The Italian experiment shows that mefloquine used as a prophylactic was very effective during the 90’s. Since then, there has been no additional data.
The French Health Monitoring Institute classifies Mozambique in group 3 of «countries with a high level of resistance to chloroquine or multiple resistance» (73). 
This means that the following recommended chemical prophylaxis is: 
- for adults: atovaquone + proguanil combination, mefloquine or doxycycline.
- for pregnant women: atovaquone + proguanil combination or mefloquine (we need to remember that cyclins are strictly contra-indicated in pregnant women.
- for children: atovaquone + proguanil combination, mefloquine or doxycycline at doses suitable for their weight.
Given the hyper-endemic nature of malaria in the country, we can only approve these recommendations. However, simple measures of individual protection against anopheline bites are to be remembered: skin repellants and persistent insecticide-treated mosquito nets for beds. 

Little data is available on Plasmodium falciparum chemoresistance. Available data seems to indicate significant resistance to chloroquine and to the sulfadoxine-pyrimethamine combination.
The Italian experiment shows that mefloquine used as a prophylactic was very effective during the 90’s. Since then, there has been no additional data.
The French Health Monitoring Institute classifies Mozambique in group 3 of «countries with a high level of resistance to chloroquine or multiple resistance» (73). 
This means that the following recommended chemical prophylaxis is: 
- for adults: atovaquone + proguanil combination, mefloquine or doxycycline.
- for pregnant women: atovaquone + proguanil combination or mefloquine (we need to remember that cyclins are strictly contra-indicated in pregnant women.
- for children: atovaquone + proguanil combination, mefloquine or doxycycline at doses suitable for their weight.
Given the hyper-endemic nature of malaria in the country, we can only approve these recommendations. However, simple measures of individual protection against anopheline bites are to be remembered: skin repellants and persistent insecticide-treated mosquito nets for beds. 

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