Jaime Carmona-Fonseca

Therapeutic efficacy test in malaria falciparum in Antioquia, Colombia

ObjectiveEvaluate the frequency of failure of eight treatments for non-complicated malaria caused by Plasmodium falciparum in patients from Turbo (Urabá region), El Bagre and Zaragoza (Bajo Cauca region), applying the 1998 protocol of the World Health Organization (WHO). Monotherapies using chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ) and sulphadoxine-pyrimethamine (SP), and combinations using chloroquine-sulphadoxine-pyrimethamine (CQ-SP), amodiaquine-sulphadoxine-pyrimethamine (AQ-SP), mefloquine-sulphadoxine-pyrimethamine (MQ-SP) and artesunate-sulphadoxine-pyrimethamine (AS-SP), were examined.MethodologyA balanced experimental design with eight groups. Samples were selected based on statistical and epidemiological criteria. Patients were followed for 21 to 28 days, including seven or eight parasitological and clinical evaluations, with an active search for defaulting patients. A non-blinded evaluation of the antimalarial treatment response (early failure, late failure, adequate response) was performed.ResultsInitially, the loss of patients to follow-up was higher than 40%, but the immediate active search for the cases and the monetary help for transportation expenses of patients, reduced the loss to 6%. The treatment failure was: CQ 82%, AQ 30%, MQ 4%, SP 24%, CQ-SP 17%, AQ-SP 2%, MQ-S-P 0%, AS-SP 3%.ConclusionThe characteristics of an optimal epidemiological monitoring system of antimalarial treatment response in Colombia are discussed. It is proposed to focus this on early failure detection, by applying a screening test every two to three years, based on a seven to 14-day follow-up. Clinical and parasitological assessment would be carried out by a general physician and a field microscopist from the local hospital, with active measures to search for defaulter patients at follow-up.

Diagnosis of gestational, congenital, and placental malaria in Colombia: comparison of the efficacy of microscopy, nested polymerase chain reaction, and histopathology.

The technical capability of different methods to diagnose Plasmodium in maternal peripheral blood, placenta, and umbilical cord blood has not been assessed in Colombia and seldom explored in other malaria-endemic regions. We designed a study to compare the technical and the operational-economical performances of light microscopy (LM), nested polymerase chain reaction (nPCR), and histopathology (HP). In maternal blood, LM had 41% sensitivity and 100% specificity and in placental blood, 35% and 100%, respectively, compared with nPCR. In placental tissue, LM had 33% sensitivity and 95% specificity; and nPCR 47% and 77%, respectively; compared with HP. Light microscopy had the best operational-economical qualification. We concluded that nPCR and HP performed better compared with LM, but field implementation of these two techniques remains a problem. Therefore, LM is recommended as the gold standard for diagnosis of gestational malaria and placental blood infection in the field.

Resistance of Plamodium falciparum to antimalarial drugs in Zaragoza (Antioquia, Colombia), 1998

Plasmodium falciparum sensitivity to chloroquine (CHL), amodiaquine (AMO) and sulfadoxine/pyrimethamine (SDX/PYR) was assessed in vivo and in vitro in a representative sample from the population of Zaragoza in El Bajo Cauca region (Antioquia-Colombia). There were 94 patients with P. falciparum evaluated. For the in vivo test the patients were followed by clinical examination and microscopy, during 7 days. The in vitro test was performed following the recommendations of the World Health Organization. The in vivo prevalence of resistance to CHL was 67%, to AMO 3% and to SDX/PYR 9%. The in vitro test showed sensitivity to all antimalarials evaluated. Concordance for CHL between the in vivo and in vitro tests was 33%. For AMO and SDX/PYR, the concordance was 100%. We conclude that a high percentage of patients are resistant to CHL (in vivo). A high rate of intestinal parasitism might explain in part, the differences observed between the in vivo and the in vitro results. Therefore, new policies and treatment regimens should be proposed for the treatment of the infection in the region. Nationwide studies assessing the degree of resistance are needed.

High genetic polymorphism of relapsing P. vivax isolates in northwest Colombia.

Graphical abstract Highlights ► Microsatellite markers were used to genotype P. vivax in of Colombia. ► A total 54 haplotypes in 58 paired (primary-recurrence/relapse) samples were found. ► Polymorphism in samples from endemic area was high. ► Relapsing and primary isolates had a different genetic conformation. ► The selected markers are useful to study P. vivax populations in the country.

Prevention of Plasmodium vivax malaria recurrence: efficacy of the standard total dose of primaquine administered over 3 days.

BACKGROUND The standard total dose (STD) of primaquine to prevent Plasmodium vivax recurrence is 0.25mg/kg day administered over 14 days (STD-14). We evaluated, in an endemic zone of Colombia, the anti-recurrence efficacy of the STD dose administered over 3 and 14 days, and of sub-STD dose administered over 3 days (71%STD-3, 50%STD-3). METHODS A controlled clinical trial was carried out with 188 subjects allocated into one of four treatment groups: STD-14, STD-3, 71%STD-3, 50%STD-3. RESULTS Recurrences during the 120 days of follow-up were 15% in STD-14, and 57% in STD-3. Treatment with 71%STD-3 and 50%STD-3 resulted in recurrence in >48% subjects within 120 days after the primary episode. High daily doses (1.17 mg/kg day) were well tolerated. CONCLUSIONS (a) The standard dose and regimen (STD-14) of primaquine to prevent P. vivax relapse is recommended. The administration of the same dose over 3 days (STD-3) should be avoided; (b) doses lower than the STD doses administered over 3 days are ineffective in preventing relapse.

Molecular Detection of Malaria at Delivery Reveals a High Frequency of Submicroscopic Infections and Associated Placental Damage in Pregnant Women from Northwest Colombia

Plasmodium infection in pregnancy causes substantial maternal and infant morbidity and mortality. In Colombia, both P. falciparum and P. vivax are endemic, but the impact of either species on pregnancy is largely unknown in this country. A cross-sectional study was carried out with 96 pregnant women who delivered at their local hospital. Maternal, placental, and cord blood were tested for malaria infection by microscopy and real-time quantitative polymerase chain reaction (qPCR). A high frequency of infection was detected by qPCR (45%). These infections had low concentrations of parasite DNA, and 79% were submicroscopic. Submicroscopic infections were associated with placental villitis and intervillitis. In conclusion, the overall frequency of Plasmodium infection at delivery in Colombia is much higher than previously reported. These data prompt a re-examination of the local epidemiology of malaria using molecular diagnostics to establish the clinical relevance of submicroscopic infections during pregnancy as well as their consequences for mothers and newborns.

Efecto de la infección submicroscópica o policlonal de Plasmodium falciparum sobre la madre y el producto de la gestación: revisión sistemática

BACKGROUND Malaria in pregnancy causes substantial maternal and infant morbidity-mortality, even at submicroscopic parasite levels. In addition, the presence of polyclonal infections secondary to high parasite genetic diversity is a common finding. OBJECTIVES To determine the frequency of submicroscopic and/or polyclonal plasmodial infection during pregnancy and to establish their impact on clinical presentation, immunity acquisition, and consequences on mother and gestation product. METHODS A search on Medline was performed using key words (MeSH): pregnancy, malaria, PCR, microscopy, genotype, and clones. Studies on plasmodial infection diagnosed by microscopy and PCR were selected. RESULTS A total of 16 studies were included, all carried out in Africa. The weighted mean (WM) of submicroscopic infection was 36%. According to type of infection (microscopic, submicroscopic or negative), the WM of maternal anemia and low birth weight (LBW) were 51%, 42%, 33%, and 19%, 16%, 11%, respectively. Risks (OR), using the negative group as reference, were: a) for maternal anemia 2.12 in microscopic infection and 1.48 in submicroscopic; b) for LBW 1.89 in microscopic and 1.56 in submicroscopic infection. The WM of polyclonal infection was 75% and the mean number of clones by sample was three. CONCLUSIONS Submicroscopic and polyclonal P. falciparum infections during pregnancy are very common, but have been little studied and their impact must be assessed in each specific region because they depend on malaria transmission intensity and stability, maternal age and parity, among other variables, which are influenced by environmental and socio-economic conditions of each region.

Placental Malaria in Colombia: Histopathologic Findings in Plasmodium vivax and P. falciparum Infections

Studies on gestational malaria and placental malaria have been scarce in malaria-endemic areas of the Western Hemisphere. To describe the histopathology of placental malaria in Colombia, a longitudinal descriptive study was conducted. In this study, 179 placentas were studied by histologic analysis (112 with gestational malaria and 67 negative for malaria). Placental malaria was confirmed in 22.35%, 50.0% had previous infections, and 47.5% had acute infections. Typical malaria-associated changes were observed in 37%. The most common changes were villitis, intervillitis, deciduitis, increased fibrin deposition, increased syncytial knots, mononuclear (monocytes/macrophages and lymphocytes), polymorphonuclear cell infiltration, and trophozoites in fetal erythrocytes. No association was found between type of placental changes observed and histopathologic classification of placental malaria. The findings are consistent with those reported for placental malaria in other regions. Plasmodium vivax was the main parasite responsible for placental and gestational malaria, but its role in the pathogenesis of placental malaria was not conclusive.

Submicroscopic infection of placenta by Plasmodium produces Th1/Th2 cytokine imbalance, inflammation and hypoxia in women from north-west Colombia

BackgroundA large-scale study was set up in order to study the epidemiology, clinical aspects, and immunopathology of gestational and placental malaria in north-west Colombia. In this region, recent reports using a qPCR technique, confirmed frequencies of infection, by Plasmodium falciparum or Plasmodium vivax, up to 45%. Given the high rates of infection observed both in mother and placenta, a first exploratory study was proposed in order to characterize the effect on the inflammation status, tissue damage and hypoxia in Plasmodium spp. infected placentas.MethodsA descriptive, prospective, cross-sectional design was applied to pregnant women with (PM+) and without (PM-) placental malaria. Messenger RNA expression of Fas, FasL; COX-1, COX-2, HIF, VEGF, and the cytokines IL-2, IL-4, IL-10, IFN-γ and TNF, were measured in peripheral and placental blood using a quantitative PCR. The percentage of apoptotic cells was determined with a TUNEL assay.ResultsIn total 50 placentas were studied: 25 were positive for submicroscopic infection and 25 were negative for Plasmodium infection. Expression of IL-4 and IL-10 was observed high in placental tissue of PM+, while IL-2 was high in peripheral blood of the same group. Expression of TNF and IFNγ in peripheral blood of the PM + group was high. Similarly, the apoptotic index and Fas expression were significantly high in PM+. However, FasL expression was observed low in PM + compared to PM-. Inflammation markers (HIF, VEGF) and hypoxia markers (COX-1, COX-2) were high in the PM + group.ConclusionDuring placental malaria expression of some pro-inflammatory cytokines is up-regulated and markers of hypoxia and tissue damage are increased in cases of submicroscopic infection.

Prevalence of gestational, placental and congenital malaria in north-west Colombia

BackgroundThe frequency of pregnancy-associated malaria is increasingly being documented in American countries. In Colombia, with higher frequency of Plasmodium vivax over Plasmodium falciparum infection, recent reports confirmed gestational malaria as a serious public health problem. Thick smear examination is the gold standard to diagnose malaria in endemic settings, but in recent years, molecular diagnostic methods have contributed to elucidate the dimension of the problem of gestational malaria. The study was aimed at exploring the prevalence of gestational, placental and congenital malaria in women who delivered at the local hospitals of north-west Colombia, between June 2008 and April 2011.MethodsA group of 129 parturient women was selected to explore the prevalence of gestational, placental and congenital malaria in a descriptive, prospective and transversal (prevalence) design. Diagnosis was based on the simultaneous application of two independent diagnostic tests: microscopy of thick blood smears and a polymerase chain reaction assay (PCR).ResultsThe prevalence of gestational malaria (thick smear /PCR) was 9.1%/14.0%; placental malaria was 3.3%/16.5% and congenital malaria was absent. A history of gestational malaria during the current pregnancy was significantly associated with gestational malaria at delivery. Plasmodium vivax caused 65% of cases of gestational malaria, whereas P. falciparum caused most cases of placental malaria.ConclusionsGestational and placental malaria are a serious problem in the region, but the risk of congenital malaria is low. A history of malaria during pregnancy may be a practical indicator of infection at delivery.