[A misleading case of hypereosinophilia revealing colonic adenocarcinoma in a patient from a tropical area]. / Une hyperéosinophilie trompeuse en milieu tropical. Hyperéosinophilie paranéoplasique.

Although paraneoplastic hypereosinophilia has been documented in patients with colon cancer, this association is rare. The purpose of this report is to describe a case of paraneoplastic hypereosinophilia associated with colic adenocarcinoma. This case underlines the value of methodical investigation of hypereosinophilia in tropical areas where parasitic aetiologies are frequent.

[Evidence of an urban, local transmission of malaria in Antananarivo, Madagascar]. / Mise en évidence d'une transmission urbaine autochtone du paludisme à Antananarivo, Madagascar.

Madagascar presents a large heterogeneity in terms of climate and altitude, which explains the uneven spread of malaria throughout the island. The capital, Antananarivo, counts more than one million inhabitants, altitude between 1250 and 1470 m, in an area where the transmission is low but malaria may cause deadly epidemic outbreaks. Numerous malaria cases are reported, without biological confirmation, and reliable data about urban malaria transmission are lacking. The " Institut Pasteur de Madagascar" together with the Malagasy Ministry of Health performed in 2003 a study about malaria transmission in Antananarivo. A prevalence survey of malaria among fever syndromes, with data collected from 43 urban dispensaries, showed that confirmed malaria cases represented only 2% of the total fever cases (15 cases out of 779 fever syndromes). The vast majority was imported from costal areas (13 cases out of 15), where malaria is hyperendemic. However, a local urban transmission was found for two patients and five other subjects identified during a proximity survey. Vectors A. arabiensis and A. funestus were found inside the patient houses, located in close proximity of flooded rice fields. Genetic analysis of P. falciparum strains allowed to distinguish three genotypes, aggregated by house. The analysis of parasite genome polymorphism proves here its validity for epidemic surveys in areas where malaria is unstable, with no premunition in the local urban population.

[Malaria in the central highlands of Madagascar: control strategies]. / Paludisme sur les hautes terres centrales de Madagascar: stratégies de lutte.

The purpose of this article is to present data on malaria in the central highland plateaux of Madagascar and strategies to improve the national malaria control program. Use of rapid diagnosis strips, early home-based fever management with pre-packaged chloroquine treatment kits and proposed new therapeutic combination based on artemisinine are discussed for management of patients with high suspicion of malaria attack. Preventive measures including alternated targeted and full-house indoor spraying for vector control, use of insecticide-impregnated bednets, implementation of intermittent preventive treatment in risk groups, optimization of the epidemic early detection and warning system using the Lot Quality Assurance Sampling method for epidemiological investigation if the alert threshold is exceeded, and provision of rapid diagnosis strips are presented.

Replacement of streptomycin by ethambutol in the intensive phase of tuberculosis treatment: no effect on compliance.

SETTING: Seven tuberculosis clinics in the National Tuberculosis Programme of Madagascar. OBJECTIVE: To compare the treatment efficacy and tolerance of regimens including either streptomycin or ethambutol for patient compliance during initial treatment of smear-positive tuberculosis. DESIGN: The 1023 patients included in the study were randomly divided into two treatment groups-one to receive streptomycin (S), isoniazid (H), rifampicin (R) and pyrazinamide (Z) (SHRZ), and the other to receive EHRZ, where streptomycin was replaced by ethambutol (E). During the 2-month intensive phase, drug delivery was completely supervised. The same 6-month continuation regimen was then given in both groups. Follow-up consisted of a clinical and bacteriological examination at the end of the second, fifth and eighth months. RESULTS: There was no significant difference between the two regimens as regards compliance with treatment, the number of patients lost or who died, or for bacteriological response during the intensive phase. EHRZ was better tolerated. During the continuation phase, the results of the two groups remained comparable, but treatment failures occurred earlier in the patients who had received streptomycin. CONCLUSION: Patient compliance was not better with streptomycin. The ethambutol-containing regimen was as efficient as the other, and better tolerated. There is no argument for preferring streptomycin in the intensive phase of treatment of smear-positive tuberculosis.

Reversibility of Schistosoma mansoni-associated morbidity after yearly mass praziquantel therapy: ultrasonographic assessment.

A parasitological, clinical and ultrasonographic longitudinal study was undertaken in 1993 in a focus hyperendemic for Schistosoma mansoni infection in the central highlands of Madagascar. All the inhabitants were systematically treated with praziquantel. A complete examination and treatment were repeated each year. Among the 289 villagers who underwent the complete 3 years' follow up, 65.9% excreted eggs at the initial survey and the mean egg count of infected individuals was 202 eggs/g. In 1996, the prevalence of infection was 19.3% with a mean egg count of 27 eggs/g and, among inhabitants aged > 44 years, only one was found to be infected. The proportion of individuals complaining of bloody stool decreased from 24.9% in 1993 to 8.4% in 1996. Compared to the initial clinical examination, the age-adjusted prevalence of splenomegaly was significantly lower in 1996, but remained high: 62% in the 10-14 years age group and 59% in individuals aged > 24 years. Ultrasonographic examination after 3 years of praziquantel therapy showed a marked decrease of the overall prevalence of schistosomal hepatic fibrosis, from 28% in 1993 to 10.3% in 1996. This improvement had already been achieved during the second year of follow-up for most subjects. Usually, the reversal of morbidity affected individuals classified as stage 1 at the beginning of the study. Stage 3 was not observed in the last 2 surveys. One patient's ascites disappeared during the follow-up, associated with a significant reversal of periportal fibrosis. Our results indicate that repeated praziquantel therapy can lead to improvement of liver morbidity and the prevention of the development of schistosomal hepatic fibrosis, even in an old-established hyperendemic focus.

South-East Asian ovalocytosis among the population of the Highlands of Madagascar: a vestigé of the island's settlement.

In the Madagascar Highlands, 0.76% of children from 168 random primary schools, and 19 of 150 families from 3 villages, had oval-shaped erythrocytes. Most harboured the deletion in the band 3 gene characteristic of South-East Asian ovalocytosis. This genetic trait supports the Indonesian origin of the Madagascar settlement.

Validity of Lot Quality Assurance Sampling to optimize falciparum malaria surveys in low-transmission areas.

To control the reappearance of malaria in the Madagascan highlands, indoor house-spraying of DDT was conducted from 1993 until 1998. Before the end of the insecticide-spraying programme, a surveillance system was set up to allow rapid identification of new malaria epidemics. When the number of suspected clinical malaria cases notified to the surveillance system exceeds a predetermined threshold, a parasitological survey is carried out in the community to confirm whether or not transmission of falciparum malaria is increasing. Owing to the low specificity of the surveillance system, this confirmation stage is essential to guide the activities of the control programme. For this purpose, Lot Quality Assurance Sampling (LQAS), which usually requires smaller sample sizes, seemed to be a valuable alternative to conventional survey methods. In parallel to a conventional study of Plasmodium falciparum prevalence carried out in 1998, we investigated the ability of LQAS to rapidly classify zones according to a predetermined prevalence level. Two prevalence thresholds (5% and 15%) were tested using various sampling plans. A plan (36, 2), meaning that at least 2 individuals found to be positive among a random sample of 36, enabled us to classify a community correctly with a sensitivity of 100% and a specificity of 94%. LQAS is an effective tool for rapid assessment of falciparum malaria prevalence when monitoring malaria transmission.

Malaria in the highlands of Madagascar after five years of indoor house spraying of DDT.

The central region of Madagascar is a vast area of highlands (altitude 700-2000 m). Malaria transmission has re-established itself here since the last epidemic of 1985-90 and has caused the deaths of 40,000 persons according to the Minister of Health. To combat the main malaria vector in the region, Anopheles funestus, annual programmes of indoor house spraying of DDT were carried out between December 1993 and January 1998 in most rural areas at altitude 1000-1500 m. A parasitological and serological study was then conducted in the highland schools to evaluate the impact of the programme and set up a database on the region. Using a cluster-sampling method 2 independent selections were conducted (one of 130 sites, the other of 40 sites). During the study, 13,462 schoolchildren were examined, 71% living in sprayed villages. Parasite prevalence among schoolchildren declined as altitude increases, from 11% at 700-900 m to 0.4% at > 1500 m. Below 1500 m, the impact of the spraying on the prevalence of the parasite was very clear (an average decrease of from 20% to 2.7% below 1000 m and of from 4.5% without spraying to 0.8% at 1000-1500 m). Geographical analysis of the data showed that the marginal regions remained the most affected by malaria (especially outside spraying zones), and persistence of 'pockets of transmission' at 1000-1500 m, essentially in areas where spraying has never been used. In 9 schools, anti-Plasmodium antibodies were sought by indirect immunofluorescence on thick smears of parasitized red blood cells. The seroprevalence ranged from 22% to 63%, which suggests that the parasite is still circulating in the region. Even though our data show that vector control continues to be very successful in the Madagascan highlands, rapid reinfection could occur and must be monitored following spraying. To this end, the Minister for Health, with the support of the Italian Co-operation, has placed the region under epidemiological surveillance since 1997. An alert system for the timely detection of the sources of epidemics and the targeting of the antivectoral campaign is also in operation. Our study suggests that this strategy should be reinforced by the spraying of DDT in the marginal zones in order to consolidate the results obtained at higher altitudes.

Radiotherapy as palliative treatment for metastatic melanoma.

This study aimed to assess the response rate and efficacy of palliative radiation therapy in patients with metastatic melanoma. From 1993 to 1999, 28 patients with 35 irradiated areas were treated with palliative radiotherapy for metastatic melanoma in the Radiotherapy Department of the Henri Mondor University Hospital, Créteil, France. Of these, 19 (68%) patients had bone and soft tissue metastases, seven (25%) patients had brain metastases and two (7%) patients had both types of metastases. Most of the patients were treated with 30 Gy of irradiation in 10 fractions over 2 weeks or 20 Gy in five fractions over 1.5 weeks. Of those with bone metastases, 67% responded to palliative bone treatment with good pain relief and/or decompression. Of the patients with brain metastases, 57% had amelioration of neurological function deficits, 29% did not respond, and one patient showed aggravation of his disease and did not finish the course of irradiation. Two patients with unresectable disease obtained partial remission and good palliation of symptoms. In conclusion, short-course radiotherapy has a role to play in the palliation of metastatic melanoma, with good relief of symptoms.

In vitro sensitivity of Plasmodium falciparum to amodiaquine compared with other major antimalarials in Madagascar.

Chloroquine has been used in Madagascar since 1945 and remains the first-line treatment for uncomplicated cases of malaria. Low-grades of resistance type R1 and R2 have been reported. Thus, in vitro tests were performed in order to monitor the drug sensitivity of Plasmodium falciparum from different study sites, with the aim of identifying alternatives to chloroquine. Chloroquine IC50 values ranged from 0.2 nM to 283.4 nM (n = 190, mean IC50 = 52.6 nM; 95% CI = 46.1-59.1 nM). Fifteen isolates (7.9%) were chloroquine-resistant. One mefloquine-resistant isolate was detected (1/139). The test isolates were sensitive to amodiaquine (n = 118), quinine (n = 212), pyrimethamine (n = 86) and cycloguanil (n = 79). The median IC50 for amodiaquine was 12.3 nM (mean IC50 = 15.3 nM, 95% CI = 13.3-17.3 nM). Amodiaquine was 3.4 times as active as chloroquine in vitro and 7 times as active as quinine against P. falciparum. These results indicate that amodiaquine may be a potent alternative to chloroquine in Madagascar. There was positive correlation between tested quinoline-containing drugs activities, which suggests in vitro cross-susceptibility.

Efficacy of artemether-lumefantrine treatment in patients with acute uncomplicated Falciparum malaria in Mayotte, a French collectivity of the Comoros Archipelago.

Mayotte is a French island located in the Comoros archipelago in the Indian Ocean. Due to the high level of resistance to chloroquine and sulfadoxine-pyrimethamine in this area, new therapeutic strategies are required. The aim was to assess and to document the efficacy of artemether-lumefantrine (AL) combination in four oral dosages. The follow-up was carried out during 21 days to monitor the antimalarial drug efficacy in an open trial in April-May, 2002. Results were obtained from 51 patients, aged from three to 46 years (12% less than five years). No case of therapeutic failure was observed. At day 2 after treatment, all the patients were apyretic and none of them had parasitaemia until day 21. This first therapeutic trial of the AL combination in the Indian Ocean sub-region shows that this association is safe, effective and rapid. AL should be an alternative treatment of uncomplicated malaria attacks in Comoros Archipelago, and will be of help to manage imported chloroquine-resistant falciparum malaria strains in Madagascar.

[Prevalence of hepatitis C virus infection in the general population of Madagascar]. / Prévalence de l'infection par le virus de l'hépatite C en population générale à Madagascar.

The achievement of a sera collection representative for the general population > or = 1 year in 1994 allowed the assessment of the seroprevalence of Hepatitis C virus infection (HCV) in Antananarivo and Toamasina provinces which represent 45% of the total population of Madagascar. The overall sero-prevalence was 1.2% among the 921 tested sera. The prevalence was not significantly different according to sex, but it increased according to the age. The absence of positive children was an argument in consideration of the low importance of mother-to-infant transmission in the epidemiology of HCV. A significant relationship was observed with past history of blood transfusion. This point is a well established idea that reminds the interest of the detection of positive individuals for anti-HCV antibodies. The seroprevalence observed in our study could be considered as moderate. It is close to the values recorded in Europe or in Japan, and much lower than those observed in Equatorial Africa.

[Epidemiological aspects of Burkitt's lymphoma in children of Madagascar]. / Aspects épidémiologiques du lymphome de Burkitt de l'enfant à Madagascar.

RATIONALE: Burkitt lymphoma (LB), a frequent, very progressive cancer with multiple factors, can be cured. However, the mortality rate remains high in Madagascar. OBJECTIVE: To analyse the epidemiological aspects of LB as well as related socio-economical issues in order to improve successful treatment of the disease. METHODS: Retrospective study of files for children aged under 15 years, hospitalised for LB in the Antananarivo oncology unit from October 1985 to June 2000. The inclusion criteria were anatomo-pathological, clinical and/or X-ray results. Studied parameters included age, sex, ethnic group, medical history, and the distance covered by the child before his/her hospitalisation. FINDINGS: The 77 cases of LB represented 16% of all children aged under 15 years seen in the hospital. The characteristics of the cases corresponded to those of African endemic LB. Most of the children with LB came from areas with endemic malaria, the Eastern and the Centre of Madagascar. All of them belonged to underprivileged families. Early medical advice was sought but distance from services delayed treatment. Various units referred the children, but especially oral surgeons (stomatologists) and ORL physicians. CONCLUSION: A strategy to ensure rapid treatment for children suffering from LB should be developed, from their region of origin up until treatment. This should involve parents as well as all members of the medical staff in charge of these children.

[Burkitt's lymphoma in children of Madagascar. Anatomo-clinical forms, therapeutic and evolutive aspects]. / Le lymphome de Burkitt de l'enfant à Madagascar. Formes anatomo-cliniques, aspects thérapeutiques et évolutifs.

RATIONALE: Burkitt Lymphoma (LB), a very progressive malignant lymphoma, can now be cured by chemotherapy. However, protocols used currently by developed countries are costly and can cause problems of tolerance for underprivileged children. OBJECTIVE: To develop a protocol of care for Malagasy children suffering from LB. METHODS: A retrospective study of the files of children aged under 15 aged years, hospitalised for LB with anatomo-pathological evidence, in the Antananarivo Oncology Unit from October 1985 to June 2000. Clinical characteristics, (paraclinical) investigations, treatment and responses to treatment were studied. FINDINGS: 40 medical records included a LB anatomo-pathological evidence. The mean age of children was 7.5 years, with a sex ratio in favour of males. All children were underweight. Maxillo-facial tumours prevailed. Other locations for tumours had also been observed, both unique or immediately multiple. Patients seem to have arrived at the hospital in the early stages of the disease, but lack of investigation probably introduced biases to the evaluation of these stages. Chemotherapy, even though incomplete due to its cost, remained the main means of treatment. Generally speaking, an immediate, favourable response was obtained, but the toxicity of chemotherapy, especially haematological toxicity, contributed to malnutrition. Overall results indicated an immediate mortality rate of 22.5%, but there was loss of follow-up for many patients. CONCLUSION: A specific protocol of LB care in Madagascar appears to be possible. Such a protocol should be based on experience with treatments, and should take into account disease characteristics, the response of Malagasy children to the treatment, as well as the country's economic state.

[Seroprevalence of viral hepatitis B in the city of Mahajanga, Madagascar in 1999]. / Séroprévalence de l'hépatite virale B dans la ville de Mahajanga à Madagascar en 1999.

A seroepidemiological study was carried out to assess the prevalence of hepatitis B virus (HBV) in the city of Mahajanga, Madagascar in July 1999. A total of 654 serum samples were collected from randomly selected subjects over the age of 2 years. The ELISA technique was used to detect serum markers of HBV infection. Prevalence rates were 14.2 p. 100 for HBs, 1.4 p. 100 for HBe antigens, and 49.5 p. 100 for HBV infection as defined by the presence of at least one serum markers. HBs antigens were detected in 20.8 p. 100 of children between the ages of 2 and 4 years and 15.3 p. 100 of women of childbearing age. In the latter age group, 5.6 p. 100 demonstrated HBe antigens, which are considered as a replication marker. The findings of this study are in agreement with those of a previous study in Madagascar and indicate that an expanded program of immunization against hepatitis B virus is warranted.

[79 cases of invasive cancer of the cervix uteri in the Department of Oncology in Antananarivo. Can diagnostic delays be improved?]. / Etude de 79 dossiers de cancers invasifs du col utérin dans le Service de cancérologie d'Antananarivo. Peut-on améliorer les délais diagnostiques?

The frequency of invasive cervical carcinoma in Western countries is currently decreasing. The development of methods of early diagnosis has improved the prognosis of the disease. In Madagascar, like in other African countries, invasive cervical carcinoma is the first genital cancer affecting women. The diagnosis comes late. Actions can be taken to improve the prognosis through early diagnosis of invasive cervical carcinoma. Our purpose was to analyze the main causes leading to these delays in diagnosis and to evaluate possibilities for improvement. This study was retrospective, consecutive and open wide not random, dealing with 79 cases of invasive cervical carcinoma, all confirmed by a histological examination, picked from the Department of Oncology at Antananarivo within a period of 24 months from the 1st of January 1990 through the 1st of January 1992. The Department of Oncology at Antananarivo is the only anti-cancer center available on the island. The position for an oncologist was occupied form 1984 to 1988 by a French doctor under the Technical Cooperation Agreement with France. Since then, no oncologist has been practicing in Madagascar. We evaluated the different reasons that could explain the delays in diagnosis and suggested possible actions to remedy the problem. We selected medical, human and technical, as well as geographical and social criteria for evaluation. Diagnosis was delayed too much (on average, about 8.48 +/- 7.12 months), possibly due to the above mentioned criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

[Profile of the patients lost to treatment in the National Anti-Tuberculosis Program in Madagascar]. / Profil des malades perdus de vue en cours de traitment dans le Programme national de lutte contre la tuberculose à Madagascar.

A national anti-tuberculosis program has been in operation in Madagascar since 1991. Despite the significant efforts made in the management, education and surveillance of patients, the number of patients lost to treatment remains high (18.8%). Noncompliance with treatment is the principal cause of treatment failure and of the development of resistance to tuberculosis drugs. This study investigated the profile of the patients who discontinue treatment. The study population consisted of the patients withdrawing from a clinical trial carried out between August 1994 and September 1996. The aim of the trial was to compare several treatments in routine practice conditions in Madagascar. The treatments tested were streptomycin (S) or ethambutol (E) associated with isoniazid (H), rifampicin (R) or pyrazinamide (Z) for the first two months, followed by 6 months of treatment H and thiacetazone (T). The trial involved four public and three private diagnosis and treatment centers in Antananarivo, Fianarantsoa and Mahajanga. A total of 1, 023 patients were included in the trial and 192 (18.8%) withdrew during the eight-month treatment period. We tracked down 109 of these patients (56.8%) and 19 patients came back to the treatment center on their own initiative for a checkup. The rate of response to a recall letter sent by mail was low. The 106 patients interviewed mostly gave professional, financial or family reasons for discontinuing treatment. Many patients stopped the treatment as soon as they began to feel better. To reduce the number of patients discontinuing treatment, the National Anti-Tuberculosis Program should improve the education of patients and their families.

Seroepidemiology of human plague in the Madagascar highlands.

We conducted a seroepidemiological survey of human plague in the general population using random sampling in the area of Ambositra, the main focus of plague in the central highlands of Madagascar (520 confirmed and presumptive cases notified during the past 10 years). Sera were tested using an ELISA IgG F1 assay. Considering the internal validity of the assay and the sampling method, the overall corrected prevalence of F1 antibodies was 0.6% (95% CI: 0.2%-1.8%). Being nearly 0 up to the age of 40, the corrected prevalence increased markedly after 45 years to 6.2%. Six of 20 individuals who declared to have been treated for clinical suspicion of bubonic plague in the past had F1 antibodies. The seroprevalence did not differ according to gender except in individuals > 60, where antibodies were significantly more frequent in males. This study suggests that the number of clinically suspected cases of plague provided by the surveillance network was plausible, despite some true cases being missed and a significant number of false positives. We also confirm that Yersinia pestis infections may occur without marked clinical manifestations and patients may recover without treatment, in accordance with old observations of pestis minor.