The American Journal of Tropical Medicine and Hygiene - Volume 80, Issue 6, June 2009

In malaria-endemic countries in Africa, a large proportion of child deaths are directly or indirectly attributable to infection with Plasmodium falciparum. Four years after high coverage, multiple malaria control interventions were introduced on Bioko Island, Equatorial Guinea, changes in infection with malarial parasites, anemia, and fever history in children were estimated and assessed in relation to changes in all-cause under-5 mortality. There were reductions in prevalence of infection (odds ratio [OR] = 0.31, 95% confidence interval [CI] = 0.2–0.46), anemia (OR = 0.11, 95% CI = 0.07–0.18), and reported fevers (OR = 0.41, 95% CI = 0.22–0.76) in children. Under-5 mortality fell from 152 per 1,000 births (95% CI = 122–186) to 55 per 1,000 (95% CI = 38–77; hazard ratio = 0.34 [95% CI = 0.23–0.49]). Effective malaria control measures can dramatically increase child survival and play a key role in achieving millennium development goals.

The participation of vivax malaria secondary clinical was researched in a retrospective cohort of 33,414 confirmed cases occurring between 1994 and 2005 in the state of Oaxaca, Mexico. Secondary episodes occurred in 23.4% of all primary cases. An increase in secondary episodes was associated with primary cases occurring during the dry seasons (risk ratio [RR] = 1.68, 95% CI: 1.45–1.96). The incidence of secondary episodes peaked at an older age, occurred similarly in men and women mostly during low mosquito abundance, and had a uniform distribution among localities. A reduction in secondary episodes was associated with the administration of an increased dose and early administration of primaquine (RR = 0.32, 95% CI: 0.26–0.38). However, limitations to distinguish relapses from re-infections impede assessment of the new treatment effect on relapses and its contribution to malaria control in the area. These findings highlight the need for new therapeutic schemes to radical cure of P. vivax infections and operational research aimed at parasite pool elimination.

Both malaria and intestinal helminths are endemic in sub-Saharan Africa, and their co-infection occurs commonly. This cross-sectional study assessed the prevalence of malaria and intestinal helminth co-infection in a sample of > 700 pregnant women in Ghana and identified risk factors for co-infection. The prevalence of malaria infection, intestinal helminth infection(s), and co-infection was 36.3%, 25.7%, and 16.6%, respectively. Women with intestinal helminth infection(s) were 4.8 times more likely to have malaria infection. Young age, low income, being single, and being primigravid were each associated with increased odds of co-infection. These associations were present when assessed separately for primi- and multigravid women, but the strength of associations varied considerably for the two groups of women. Young age had the strongest association among both primigravid (odds ratio = 5.2) and multigravid (odds ratio = 3.2) women. This study shows relatively high prevalence rates of malaria, intestinal helminths, and co-infection in pregnant women in Ghana.

The antimalarial susceptibility of ring stage (> 80%) Plasmodium vivax from the Republic of Korea, where long incubation–period strains are prevalent, was evaluated using the schizont maturation inhibition technique. During 2005–2007, susceptibility to seven antimalarial drugs was evaluated with 24 fresh isolates. The geometric mean (95% confidence interval) 50% inhibition concentration (IC50) were quinine 60 (54–75) ng/mL, chloroquine 39 (22–282) ng/mL, piperaquine 27 (17–58) ng/mL, mefloquine 39 (35–67) ng/mL, pyrimethamine 138 (89–280) ng/mL, artesunate 0.6 (0.5–0.8) ng/mL, and primaquine 122 (98–232) ng/mL. Positive correlations were found between quinine and mefloquine (r = 0.6, P = 0.004), piperaquine and chloroquine (r = 0.6, P = 0.008), and piperaquine and primaquine IC50 values (r = 0.5, P = 0.01). Compared with P. vivax in Thailand, P. vivax in the Republic of Korea was more sensitive to quinine and mefloquine, but equally sensitive to chloroquine and artesunate.

Small-scale interventions on training medicine retailers on malaria treatment improve over-the-counter medicine use, but there is little evidence on effectiveness when scaled up. This study evaluated the impact of Ministry of Health (MoH) training programs on the knowledge and practices of medicine retailers in three districts in Kenya. A cluster randomized trial was planned across 10 administrative divisions. Findings indicated that 30.7% (95% confidence interval [CI]: 23.3, 39.0) and 5.2% (95% CI: 2.1, 10.3) of program and control retailers, respectively, sold MoH amodiaquine with correct advice on use to surrogate clients (OR = 8.8; 95% CI: 2.9, 26.9; P < 0.001). Similarly, 61.8% (95% CI: 54.2, 69.1) and 6.3% (95% CI: 2.7, 12.1) of program and control retailers, respectively, reported correct knowledge on dosing with amodiaquine (OR = 29.8; 95% CI: 8.2, 108.8). Large-scale retailer training programs within the national malaria control framework led to significant improvements in retailers’ practices across three districts.

Reports on treatment failures associated with the use of first-and second-line antimalarial drugs chloroquine and sulfadoxine-pyrimethamine have recently increased in many parts of Indonesia. The present study evaluated artemisinin-based combination therapy for treatment of persons with uncomplicated Plasmodium falciparum malaria in West Sumba District, East Nusa Tenggara Province. A total of 103 persons 1–57 years of age were enrolled, given standard artesunate-amodiaquine therapy, and followed-up for 28 days. All persons clinically recovered, but two persons were again parasitemic on day 7. This finding indicated that these two persons had recurrent parasitemias on days 21 and 28. Molecular analyses suggested both recurrences were caused by reinfections. There were no severe adverse events, but complaints of gastrointestinal upset, nausea and vomiting, and headache linked to therapy occurred among 9.7%, 5.8% and 5.8% of the persons, respectively. Artesunate-amodiaquine proved efficacious therapy for treatment of persons with uncomplicated P. falciparum malaria at one site in eastern Indonesia but it may have tolerability problems that merit further investigation.

Shortly after Kenya introduced artemether-lumefantrine (AL) for first-line treatment of uncomplicated malaria, we conducted a pre-post cluster randomized controlled trial to assess the effect of providing malaria rapid diagnostic tests (RDTs) on recommended treatment (patients with malaria prescribed AL) and overtreatment (patients without malaria prescribed AL) in outpatients ≥ 5 years old. Sixty health facilities were randomized to receive either RDTs plus training, guidelines, and supervision (TGS) or TGS alone. Of 1,540 patients included in the analysis, 7% had uncomplicated malaria. The provision of RDTs coupled with TGS emphasizing AL use only after laboratory confirmation of malaria reduced recommended treatment by 63%-points (P = 0.04), because diagnostic test use did not change (−2%-points), but health workers significantly reduced presumptive treatment with AL for patients with a clinical diagnosis of malaria who did not undergo testing (−36%-points; P = 0.03). Health workers generally adhered to RDT results when prescribing AL: 88% of RDT-positive and 9% of RDT-negative patients were treated with AL, respectively. Overtreatment was low in both arms and was not significantly reduced by the provision of RDTs (−12%-points, P = 0.30). RDTs could potentially improve malaria case management, but we urgently need to develop more effective strategies for implementing guidelines before large scale implementation.

Plasmodium knowlesi has recently been recognized as the fifth Plasmodium species causing malaria in humans. Diagnosis is difficult morphologically, and currently, available rapid tests have not been comprehensively evaluated with this pathogen. We report a case of P. knowlesi malaria that was confirmed after the initial clue of discordant microscopy and immunochromatographic results, highlighting the importance of molecular diagnostics in cases with the relevant clinical and epidemiologic history.

Accuracy of an rK39 rapid diagnostic test (DiaMed-IT-Leish ®) for visceral leishmaniasis (VL) was compared with splenic aspiration and the direct agglutination test (DAT) in a population with a high prevalence of infection with human immunodeficiency virus (HIV) in Ethiopia. There were 699 patients clinically suspected of having VL (153 parasitologically confirmed, 482 DAT confirmed, and 130 DAT negative), and 97 DAT-negative controls. A total of 84% were tested for HIV and 34% were HIV positive. Sensitivity of the rK39 test in parasitologically confirmed VL patients was 84% (77% in HIV positive and 87% in HIV negative; P = 0.25). Sensitivity of the DAT was higher (94%; P = 0.01), 89% in HIV-positive patients and 95% in HIV-negative patients; P = 0.27). Specificity of the rK39 test was 99% in DAT-negative controls and 92% in DAT-negative patients clinically suspected of having VL. A diagnostic algorithm combining DAT and the rK39 test had a sensitivity of 98% in HIV-positive VL patients and 99% in HIV-negative VL patients. Despite the lower sensitivity in a population with a high prevalence of HIV, the DiaMed-IT-Leish ® rK39 test enables decentralization of diagnosis. Patients clinically suspected of having VL who show negative results on the rK39 antigen test should undergo follow-up DAT testing, especially if they are HIV positive.

Mucosal leishmaniasis (ML) is an oral disease caused by the parasite Leishmania donovani. The disease has been proven to be pandemic in many areas of the world. It affects young men living in leishmaniasis-endemic areas. ML might be accompanied or proceeded by visceral leishmaniasis (VL), although in most of the cases seen in Sudan, ML occurs as a primary lesion. ML can mimic oral cancer or fungal infections, with ulceration as the most common finding in ML lesions. In this report, the patient came from an area known to be endemic for VL. Although the lesions were not ulcerative, the patient history was indicative for ML. Early detection and proper diagnosis were of great help in the cure and prognosis of the disease.

We report a case of drug hypersensitivity syndrome (drug reaction with eosinophilia and systemic symptoms [DRESS]) induced by parenteral meglumine antimoniate (Glucantime) in a 40-year-old man who traveled to Bolivia and was treated for mucocutaneous leishmaniasis. Two weeks after starting therapy, the patient had fever, joint pain, a cutaneous eruption, and hypereosinophilia (1,358 cells/mm3). These symptoms resolved after drug withdrawal but reappeared upon reintroduction of the drug. Pentavalent antimonials should be definitively withdrawn in patients with hypereosinophilia > 1,000 cells/mm3 accompanied by systemic manifestations consistent with DRESS.

Cyclic AMP–protein kinase A (PKA) signaling is important for the growth and differentiation of Trypanosoma cruzi. Immunofluorescence suggests that PKA can associate with the plasma membrane of trypomastigotes. We found that the PKA regulatory subunit interacts with several P-type ATPases. These P-type ATPases may play a role in anchoring PKA to the plasma membrane in T. cruzi.

Trypanosoma cruzi, the etiologic agent of Chagas disease, presents a complex life cycle, cycling between reduviid vectors and wild and domestic mammals. The European rabbit is an introduced species in America, but its role as reservoir in the wild transmission cycle of Chagas disease remains unknown. We used polymerase chain reaction, Southern blot, and hybridization tests to detect infection and characterize genotypes in rabbits from a hyperendemic area of Chagas disease in Chile. Results show 38% of infection with different genotypes. We provide evidence that rabbits are naturally infected with T. cruzi, which may have important epidemiologic consequences for the wild transmission cycle.

Serial magnetic resonance imaging (MRI) was performed up to 4 years after treatment in a patient with Trypanosoma brucei gambiense infection. Four years after treatment and cure abnormalities were still present, although the patient led a normal social life, without physical and mental impairments. The literature on MRI in human African trypanosomiasis is reviewed. The MRI is useful to discriminate between encephalitis induced by trypanosomiasis and post-treatment reactive encephalopathy, a severe and often fatal complication of treatment, in particular of treatment with arsenicals. The MRI is not useful for diagnosis of human African trypanosomiasis (HAT).

The aim was to evaluate the efficacy of Saccharomyces boulardii (Sb) in addition to metronidazole in amebiasis. A prospective, randomized, open clinical trial was performed in 50 children presenting with acute bloody diarrhea caused by Entameba histolytica. Group A and B (each N = 25) was treated with metronidazole, but Sb (250 mg, twice daily) during the 7 days was added to Group B patients who were re-evaluated 2, 3, 5, 10, and 30 days after diagnosis. Duration of bloody diarrhea was significantly longer in Group A (72.0 ± 28.5 versus 42.2 ± 17.4 hours, P < 0.001). On day 5, amebic cysts had disappeared in all children in Group B, whereas in Group A, amebic cysts were still present in 6 children (P < 0.05). On day 10, all children were cured and cysts had disappeared in all. The addition of Sb to metronidazole in amebiasis significantly decreases duration of (bloody) diarrhea and enhances clearance of cysts.

The treatment for hydrocele is expensive, invasive surgery—hydrocelectomy. A drug that could prevent or improve this condition could replace or supplement hydrocelectomy. In Ghana, 42 hydrocele patients participated in a double-blind, placebo-controlled trial of a six-week regimen of doxycycline, 200 mg/day. Four months after doxycycline treatment, patients received 150 μg/kg of ivermectin and 400 mg of albendazole, which is used for mass chemotherapy in this area. Patients were monitored for levels of Wolbachia sp., microfilaremia, antigenemia, plasma levels of vascular endothelial growth factor-A (VEGF-A) and stage/size of the hydrocele. Wolbachia sp. loads/microfilaria, microfilaremia, and antigenemia were significantly reduced in the doxycycline-treated patients compared with the placebo group. The mean plasma levels of VEGF-A were decreased significantly in the doxycycline-treated patients who had active infection. This finding preceded the reduction of the stage of hydrocele. A six-week regimen of doxycycline treatment against filariasis showed amelioration of pathologic conditions of hydrocele patients with active infection.

Neurocysticercosis, an endemic parasitic disease in most developing countries, is caused by Taenia solium and compromises the human central nervous system. Cathepsin L-like proteases are secreted by several parasites including T. solium and constitute important antigens for immunodiagnostics. A protein fraction with cathepsin L-like activity was purified from the cysticercus fluid by size exclusion and ion exchange chromatography. Cathepsin L-like activity was measured fluorometrically by detecting the hydrolysis of the fluorogenic substrate Z-Phe-Arg-AMC. The purified protein fraction included antigens of 53 and 25 kD that were tested in a Western immunoblot and in an enzyme-linked immunosorbent assay (ELISA) for detection of human cysticercosis. The sensitivity of the Western immunoblot was 96% for patients infected with multiple cysts and 78% for patients with a single cyst. Specificity was 98%. The sensitivity of the ELISA was 98% in patients with multiple cysts and 84% in patients with a single cyst. Specificity was 92.7%.

Well-funded initiatives are challenging developing countries to increase health intervention coverage and show impact. Despite substantial resources, however, major obstacles include weak health systems, a lack of reasonably accurate monitoring data, and inadequate use of data for managing programs. This report discusses how integrated continuous surveys and quality management (I-Q), which are well-recognized approaches in wealthy countries, could support intervention scale-up, monitoring and evaluation, quality control for commodities, capacity building, and implementation research in low-resource settings. Integrated continuous surveys are similar to existing national cross-sectional surveys of households and health facilities, except data are collected over several years by permanent teams, and most results are reported monthly at the national, province, and district levels. Quality management involves conceptualizing work as processes, involving all workers in quality improvement, monitoring quality, and teams that improve quality with “plan-do-study-act” cycles. Implementing and evaluating I-Q in a low-income country would provide critical information on the value of this approach.