Efficacy and safety of twice-weekly administration of three RDAs of iron and folic acid with and without complement of 14 essential micronutrients at one or two RDAs: a placebo-controlled intervention trial in anemic Cambodian infants 6 to 24 months of age.

OBJECTIVE: To determine the differential efficacy and safety of twice-weekly administration of 3 RDAs of iron and folic acid, with and without a complement of 2 RDAs of 11, and 1 RDA of 3 additional essential micronutrients as compared to a placebo control (PlbCON) given as foodLETs. SUBJECTS/METHODS: A total of 250 children aged 6-24 months were enrolled after recruitment by village health workers; 19 of them dropped out during the trial. Children were assigned to one of three treatment arms and followed for 20.5 weeks; 41 supervised twice-weekly dosings of 30 mg of iron plus folic acid, either with or without accompanying micronutrients or placebo were given as foodLETs, a tool for ready-to-eat fortification in infant food. Initial and final measurements of anthropometry and blood biomarkers for hematological, iron stores and inflammatory status, as well as for abnormal hemoglobin (Hb), were obtained. Symptoms of listlessness, vomiting, watery stools and acute respiratory infections were monitored weekly. RESULTS: Iron-containing supplements increased Hb concentrations significantly (P<0.0001) and virtually eradicated any IDA, as compared to no change in hematological status in the PlbCON group (P=0.011). Iron stores, as reflected by ferritin, increased significantly with iron-containing treatments (P<0.0001). Responses were as effective in individuals with HbE as in those with exclusively HbA phenotypes. Watery stools (P=0.002) and listlessness (P=0.001) were significantly more frequent in those receiving iron and folic acid alone than in the PlbCON group. In contrast, acute respiratory infections (P=0.014) and listlessness (P=0.001) were significantly less frequent in those receiving the multiple micronutrient formulation than in the PlbCON group. CONCLUSIONS: Supplementation of micronutrients along with iron and folic acid mitigates the excess morbidity of iron-folate alone, without reducing its efficacy in correcting anemia and building iron stores. FoodLETs are a suitable vehicle to provide micronutrient supplementation to infants.

Characterization of hepatitis B surface antigen strains circulating in the Kingdom of Cambodia.

A collection of hepatitis B surface antigen (HBsAg)-reactive serum specimens from the Pasteur Institute of Cambodia was investigated for the genotype, predicted serotype and the presence of diagnostically significant mutations in the surface protein. From a set of 794 samples, 15 were identified serologically to harbour possible HBsAg mutants and were investigated further. An additional 20 samples were included into the study for PCR and sequence analysis. Of the 22 samples which were HBV-DNA-positive, 16 were of genotype C with the remaining six being genotype B. Point mutations resulting in amino acid substitutions were noted in 10 samples. The majority of these mutations occurred outside the a determinant.

[Histology of liver lesions due to Schistosoma mekongi. About six cases with severe portal hypertension operated in Cambodia]. / Lesions histologiques hépatiques de la schistosomose due a Schistosoma mekongi. A propos de six cas avec hypertension portale sévère opérés au Cambodge.

Schistosomiasis mekongi was shown to be endemic, along the Mekong River, in northern Cambodia, affecting many patients with portal hypertension. Surgical procedures were proposed to some patients with digestive haemorrhage history to avoid fatal recurrence. The aim of our study was to evaluate the intensity of the liver fibrosis among these patients. During surgical treatment, liver biopsies were collected, fixed in Bouin or in formalin and processed at the Institut Pasteur of Cambodia. Sections were stained by H&E, Masson's trichrome, PAS, Ziehl-Neelsen's method and Congo Red. A total of six biopsies from patients aged 16-36 were analysed. There was complete disorganization of hepatic architecture with fibrous enlargement of portal tracts and some portal-portal bridging fibrosis, but there was no cirrhosis. In portal areas, there was blood vessel congestion and thrombosis with inflammation. Bile ducts were normal. In the parenchyma, congestion of sinusoidal capillaries was combined with focal mononuclear inflammatory infiltrate. There was no steatosis, no necrosis, no cholestasis, no iron accumulation and no amyloidosis. Numerous eggs of Schistosoma mekongi were observed in five cases, mostly in fibrous areas and more rarely in the parenchyma. Eggs were round or oval, measuring 60 x 40 microns with an acid-fast thin hyaline wall. Some eggs were surrounded by epithelioid and giant cell reaction. In conclusion, our findings illustrated a surprisingly high degree of fibrosis among young adults which contrasts with other schistosomiasis.

[Place of surgery in the prevention of recurrences of digestive haemorrhages at the patients presenting a portal hypertension due to Schistosoma mekongi]. / Place de la chirurgie dans la prévention des récidives d'hémorragies digestives chez les sujets présentant une hypertension portale due a Schistosoma mekongi.

In spite of a decrease of the prevalence of hepato-splenic schistosomiasis thanks to mass-treatment with Praziquentel from December 1994 till now (CNM - MSF - WHO - Health Provincial Director) of target-populations in Kratie Province, severe cases of portal hypertension are not exceptional (digestive bleedings, after rupture of oesophageal varices). Out of 106 cases of portal hypertension: alI patients have had clinical survey biological tests (liver function, haematology and serology). Most of them had ultrasonography (Aloka 55,500 Sound 3.5 MHz). Nearly half of the group of 153 patients has never had bleedings. More than 45 were not eligible for surgery for different reasons: severe anaemia (few possibilities for massive transfusion in Cambodia), serology (S. mekongi) + but also hepatitis B or C +, hepatic biological exams (hepatic insufficiency). So we decided for eleven of them to use a surgical decompression procedure in order to decrease portal hypertension and the porto-systemic gradient. After defining portal hypertension, specific clinical features of portal hypertension (secondary to Schistosomiasis) the authors report eleven cases who were operated on (2000-2002): 4 mesenterico-cave shunt with interposition of a graft (Drapanas' procedure), 1 operation of HASSAB (after splenectomy), 6 proximal spleno-renal diversion (after splenectomy). After studying the results of the eleven patients, discussion with other surgical procedures, particularly endoscopic procedures is developed. The follow-up of these patients during at least five years is mandatory to give guidelines for post-systemic shunts to prevent rebleeding (near other methods). Treated too late, schistosomiasis has no benefit from drugs (Praziquentel). After a mean period of forty two months, the following results are: mortality: one case (10 days after operation): hepatic insufficiency (group Child B/C). morbidity: one occlusion of the small intestine, after 4 months (debridment), operated at the Provincial hospital of Kratie (case no1). Ten patients resume work, family and social life between Kratie and Sambor in 2002. No rebleeding. No encephalopathy.

[Diagnosis and treatment of invasive cervical cancer in Cambodia (apropos of 35 cases)]. / Diagnostic et traitement du cancer invasif du col utérin au Cambodge (a propos de 35 cas).

Uterine cervix cancer is an important public health problem in developing countries. In Cambodia, incidence (24. 10-5) and mortality (12,77. 10-5) rates due to this cancer are higher than in other southeast Asian countries. 35 consecutive women with a diagnosis of invasive cervical cancer were identified from the histology laboratory of the Institut Pasteur in Phnom Penh. Information on history, clinical findings, ancillary investigations and treatment were obtained by clinical files review. Patients were from Phnom Penh, the main city and from outlying provinces. The mean age was 50 years, 2 months. They all presented with clinical symptoms at the time of diagnosis, and lesions had spread beyond the uterus in nearly half of the cases. Squamous cell carcinoma (80%) was more frequent than adenocarcinoma (14%). Microinvasive squamous cell carcinomas were rare (2.8%). Treatment was mainly surgical, but lacked standardization, as radical hysterectomy including lymphadenectomy was not systematic, even when the tumor spread beyond the uterine cervix. Few women that required adjuvant radiotherapy received it as this technique has only recently been introduced in Cambodia. Many patients were lost to follow-up. None of the cases was detected by pap smear. This technique is not in general use in the country. Cervical cancer screening could be carried out by visual inspection of the cervix with acetic acid wash that is less expensive and nearly as sensitive as pap smear. Treatments are still insufficiently standardized, due to the lack of technical means, and lack of patient compliance.

[Frequency of G6PD deficiency in a group of preschool-aged children in a centrally located area of Cambodia]. / Déficit en G6PD, fréquence dans un groupe d'enfants d'âge préscolaire d'une région centrale du Cambodge.

The aim of this study was to determine the frequency of G6PD deficiency and assess its impact on morbidity, especially anemia, in preschool-aged children in Cambodia. A total of 151 children including 82 boys and 69 girls from the Kandal province near Phnom Penh were studied. Ages ranged from 8 to 69 months. Blood was collected in EDTA-coated tubes. Blood counts were performed with an ABX Micros 60 system and G6PD in red blood cells was measured with a Roche Cobas Mira Plus system using Gamma reagents. G6PD deficiency was found in 14 cases (13.4% of boys and 4.3% of girls). Deficiency was complete in 7.3% of children and partial in 2%. Anemia defined as hemoglobin concentration less than 110 g/l was detected in 29.1% of children. No case of anemia could be attributed to enzyme deficiency since no sign of hemolysis was observed in any of the three children presenting both conditions. Further study is needed on G6PD deficiency in Cambodia including malaria-endemic areas and on the frequency and severity of jaundice due to enzyme deficiency in newborns.

[Prevalence of hepatitis A, B, C and E virus markers among patients with elevated levels of Alanine aminotransferase and Aspartate aminotransferase in Phnom Penh (Cambodia) and Nha Trang (Central Vietnam)]. / Prévalence de marqueurs d'infection des hépatites virales A, B, C et E chez des patients ayant une hypertransaminasémie a Phnom Penh (Cambodge) et Nha Trang (Centre Vietnam).

In order to describe the respective part of viral hepatitis in liver diseases observed in Cambodia and Vietnam, ninety consecutive patients with Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) > or = 100 Ul/l were tested for hepatitis A, B, C and E markers in Phnom Penh and Nha Trang. The markers were IgM antibodies to hepatitis A virus (anti-HAV IgM), hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCVAb) and IgG antibodies to hepatitis E virus (anti-HEV IgG). Recruited patients were predominantly adults and male (sex ratio 76%). Among these patients, 81% were tested positive to at least one marker in Nha Trang and 79% in Phnom Penh. In Nha Trang, HBsAg was more frequent (73%) than anti-HCV Ab (9%) while in Phnom Penh both markers were closely similar (HBsAg: 41%, anti-HCV Ab: 39%). In both population samples, HBsAg was more prevalent among young people whereas anti-HCV Ab were only detected in adults. No case of acute HAV infection was diagnosed in Nha Trang while anti-HAV IgM were detected in 20% of Cambodian patients. Anti-HEV IgG were infrequent (2% in Nha Trang, 5.5% in Phnom Penh). Only one case was notified, a male Vietnamese patient probably suffering from acute hepatitis E. More studies would be useful to improve the control measures against viral hepatitis in the public health programs.

[Survey of lymphatic filariasis on Ouvea Island in New Caledonia]. / Enquete sur la filariose lymphatique dans l'île d'Ouvéa en Nouvelle-Calédonie.

Several cases of Bancroftian filariasis were recently reported on Ouvea Island which is part of the archipelago of New Caledonia located in the south Pacific Ocean. Following these reports systematic screening was carried out in a group of 382 adult consultees at two medical dispensaries. Tests to detect microfilariae in the blood and antibodies in serum were performed at the Pasteur Institute in New Caledonia and the Malarde Institute in Papeete, French Polynesia, respectively. Of the two subjects with manifestations consistent with filariasis, one was seropositive but neither presented microfilariae. Overall 14 subjects (3.7 p. 100) presented microfilariae and 124 were seropositive (33.5 p. 100). The serologic index was significantly higher in men than in women (6.1 p. 100 vs 2.1 p. 100). Parasitic and serologic indexes were significantly higher (p < 0.001) in subjects living in the northern than southern part of the island. As in previous studies in New Caledonia, present data showed that Bancrofitian filariasis is asymptomatic on Ouvea Island. This finding contrasts with the symptomatic forms described on other islands in the south Pacific.

Deep-seated fungal diseases in the South Pacific, especially in New Caledonia.

The main deep-seated fungal diseases and their encountered pathology in New Caledonia and other islands of the South Pacific are reviewed (1970-96). Cryptococcosis is encountered in all islands of the South Pacific, Australia and Papua New Guinea, with a predominance of variety gattii, which is associated with some species of Eucalyptus. Histoplasmosis is not uncommon, and there was an epidemic in New Caledonia in 1994 among people who had visited a bat-inhabited cave. Mycetomas, in particular presenting as pale granules in tissues, are encountered in New Caledonia, Vanuatu, Papua New Guinea, Fiji and French Polynesia. Other fungal infections, such as zygomycosis, sporotrichosis (three cases) and chromomycosis (six cases) are rarely observed in New Caledonia.

[29 cases of malaria introduced into New Caledonia from 1992 to 1995]. / A propos de 29 cas de paludisme importé en Nouvelle-Calédonie de 1992 à 1995.

Although located in a tropical zone of the South Pacific, the island of New Caledonia is malaria-free. This retrospective study of imported malaria was conducted jointly by the Pasteur Institute of New Caledonia and the Gaston Bourret Territorial Hospital between January 1, 1992 and December 31, 1995. A total of 29 patients were hospitalized for malaria. Most contracted the disease in Vanuatu. Plasmodium vivax was involved more often than Plasmodium falciparum (22 vs. 11). No case was severe, complicated, or fatal. In most cases treatment consisted of quinine followed by mefloquine. The median duration of hospitalization was 5.7 days. Since the annual incidence of imported malaria is significantly higher in New Caledonia than in France, the authors propose that a Travelers Information Center should be set up in New Caledonia to improve prophylaxis against malaria.

Nodular breast filariasis: diagnosis by fine needle aspiration.

Bancroftian filariasis is a tropical disease transmitted by mosquitoes that most often causes lymphadenitis. This article reports on a breast nodule due to Wuchereria bancrofti in a woman living in New Caledonia. The diagnosis was done by fine needle aspiration, which showed several microfilariae and avoided surgical treatment.

Malignant pilomatrixoma of the scalp.

A 33 yr old man with a history of pilomatrixoma of the scalp, presented 5 mths later with a metastatic undifferentiated carcinoma in a submandibular lymph node. The cutaneous and lymph node tumors showed close histological similarity and features of malignancy. Investigations over 30 mths excluded a primary neoplasm elsewhere and consequently led to the diagnosis of malignant pilomatrixoma. These tumors are rare and most often located on the scalp. Most of the affected patients are middle age males. Wide excision is advised to avoid recurrences.

[Leprosy in New Caledonia from 1983 to 1992. Histopathological and epidemiological data]. / La lèpre en Nouvelle-Calédonie de 1983 à 1992. Données histopathologiques et épidémiologiques.

New Caledonia is a South Pacific Island inhabited by more than 170,000 people: most of them are melanesians or europeans. Multidrug therapy for Hansen disease has been employed since 1983; so we made an epidemiologic and histopathologic study of the new cases diagnosed for 10 years, from 1983 to 1992. Local (clinical, histological, microbiological and immunological) means of diagnosis are described. In New Caledonia, the endemic level is lower than in the small neighbouring Pacific islands but there is still a native reservoir of Mycobacterium leprae with 40% multibacillary types. Nearly half of the new cases are less than 25 years old. They are often male melanesians. The diagnosis of indeterminate forms is debated when there is no acid-fast bacillus. Border-line forms are rare. Tuberculoid leprosy poses many differential diagnosis problems. Despite available multidrug therapy, one cannot yet consider that the incidence is decreasing significantly.

[Pulmonary dirofilariasis]. / Dirofilariose pulmonaire.

Dirofilariosis usually concerns dogs among which it is transmitted by mosquito bites. Human infection is rare and we describe here a case observed in a 75 years old woman in New Caledonia. A systematic pulmonary radiograph showed suspicious pulmonary nodules. At microscopic examination one can see pulmonary infarctus with thrombosis and Dirofilaria immitis inside a vessel. Diagnosis is usually made by histologic examination because biological investigations are of a little interest. Surgical treatment is enough. Chemioprophylaxia for dogs can reduce the risks of man infection.

[Cutaneous malignant melanoma in New Caledonia (South Pacific) 1973-1991. A study of 97 cases]. / Le mélanome malin cutané en Nouvelle-Calédonie (Pacifique Sud) 1973-1991. Etude de 97 observations.

The Cancer Registries have been operational in the South Pacific since 1958 (Papua New Guinea), Fiji (1965) and New Caledonia (1977) and complete cancer incidence rates are available, based on histologic data. We studied 97 melanomas, histologically confirmed, which were diagnosed in New Caledonia from 1973 to 1991. New Caledonia is located in the same latitude as Queensland in Australia, known for having the highest incidence of melanoma in the world. Standardised incidence rates (world population) were 9.82 and 7.65/100,000/year for European males and females, compared to 1.65 and 1.05 for Melanesian and Polynesian males and females. The European population is exposed and Melanesians/Polynesians are relatively protected as are black Americans or Africans. The mixed populations are protected, but no study is available as to the exact proportion of mixed people (20%?) in the entire population. For Europeans, among males, the main areas in which melanomas occur are the trunk (45%) the arm (13%) and the leg (13%). Among females, the main areas are the leg (27%), the trunk (20%) and the head (18%). Screening for melanoma has been more effective in the last 6 years, a period in which we diagnosed half the total cases and generally at earlier stages. Prognosis was poor for this period (1973-1991): the five year survival rates were 64% +/- 8%, not as good as in Europe or Australia, but these lesions were diagnosed between 1973 and 1985 and were generally more invasive. A better prognosis will probably be observed in a few years, and another evaluation of melanoma screening should be made in the future as well the study of precursors and early lesions.

[Malignant teratoid medulloepithelioma of the ciliary body. Apropos of a case and review of the literature]. / Médullo-épithéliome tératoïde malin du corps ciliaire. Présentation d'un cas et revue de la littérature.

A case of ocular medulloepithelioma is reported and the authors review the literature concerning these rare tumors. This report concerns a ten-month-old girl in whom ophthalmic examination showed a large tumor arising in the ciliary body with such rapid progression that enucleation was necessary. Pathological findings were compatible with a malignant teratoid medulloepithelioma. According to preceding descriptions, slit lamp examination and ultrasonography are the best approach to the diagnosis. Medulloepithelioma is a tumor composed of poorly differentiated neuroepithelial cells and the predominant histological feature is a net-like pattern. Teratoid forms contain cartilage or brain tissue or bundles of skeletal muscle. The main criterion for malignancy is the presence of neuroblastic cells. Local excision is sufficient when the tumor is mall, otherwise enucleation or even exenteration may be necessary. The prognosis is generally good even when the tumor presents malignant features on pathological examination, provided treatment is instituted rapidly.