The American Journal of Tropical Medicine and Hygiene - Volume 71, Issue 1, July 2004

Lymphatic filariasis caused by infection with Wuchereria bancrofti and Brugia malayi is endemic in 45 of 77 provinces in The Philippines. To prepare the island of Mindoro for mass treatment using diethylcarbamazine and albendazole, complete census data were collected in rural villages. A sample of individuals selected from each of two adjacent villages was examined for microfilaremia. Microfilariae were detected from thin smears in 34 (13%) of 272 patients examined from the village of Bayanan and 10 (3.4%) of 292 in the village of Mangangan (P < 0.01, by chi-square test). In these villages, the majority of those infected were members of the ethnic group known as Mangyans: 33 (97%) of 24 in Bayanan and 7 (70%) of 10 in Mangangan (risk ratio = 89, 95% confidence interval = 33–240, P < 0.001.) In children examined who were less than 10 years of age (n = 165), girls were more commonly infected than boys, even though the proportion of males in the general population was greater. Understanding sociocultural characteristics and related behaviors in future observations among the Mangyan may help to explain local differences in the distribution of filariasis. This information should also be helpful in designing more culturally appropriate strategies for the control of lymphatic filariasis among ethnic minorities in The Philippines.

The nematode parasites Wuchereria bancrofti, Brugia malayi, and B. timori cause a human disease known as lymphatic filariasis, which afflicts approximately 120 million people worldwide. These organisms are known to contain endosymbiotic bacteria (Wolbachia) that are related to rickettsiae. It has been previously reported that tetracycline blocks the L3 to L4 molt of the filarial parasite B. malayi, and suggested that this was related to their known anti-rickettsial activity. However, this interpretation was tempered by several observations. First, Wolbachia DNA could still be detected in nematodes from tetracycline-treated cultures. In addition, chloramphenicol, which has anti-rickettsial and anti-chlamydial activity, failed to inhibit the molt. These observations could not rule out the possibility that the anti-molting activity of tetracycline is due to pharmacologic activities unrelated to its anti-rickettsial functions. This study shows that chemically modified tetracycline, which does not to have anti-microbial activity, also blocks molting.

CD8+ and CD4+ T cells are involved in immunity to the pre-erythrocytic stage of malaria. This study has been undertaken to define T cell epitopes on the Plasmodium vivax circumsporozoite protein (CSP) and to analyze the early induction of immune response following infection. We identified CD4+ and CD8+ T epitopes recognized by different strains of mice as well as by humans. The CD4+ T cell response in mice was found to be similar in all strains, but variation between strains was evident. Five H-2d-restricted CD8+ cytotoxic T lymphocyte (CTL) epitopes, but no H-2k-or H-2b-restricted epitopes, could be defined. Non-H-2 genes were also able to regulate the response. In recently infected Thai adults, poor immunoresponsiveness was demonstrated. CTL activity and proliferative responses of T cells from malaria-exposed donors were very low. In contrast, exposed individuals had specific antibodies against the immunodominant repeats of both common strains of the P. vivax CSP; however, titers decreased following treatment.

The polymorphisms in the Plasmodium falciparum multidrug resistance 1 (pfmdr1) and P. falciparum chloroquine resistance transporter (pfcrt) genes, which are associated with chloroquine resistance, were examined in 48 P. falciparum isolates from uncomplicated malaria patients from the West Lombok District in Indonesia. The point mutation N86Y in pfmdr1 was present in 35.4% of the isolates and mutation K76T in pfcrt was found in all but one of the samples studied. Identified pfcrt haplotypes were mainly identical to the Papua New Guinea type SagtVMNT (42 of 48, 87.5%), and a few isolates had the Southeast Asia type CVIET (5 of 48, 10.4%). Moreover, one P. falciparum isolate harbored the K76N mutation, giving rise to the haplotype CVMNN, which was not previously reported in field isolates. Our findings suggest that chloroquine resistance in this area might have the same origin as in Papua New Guinea.

Heme oxygenase (HO) is thought to be induced in severe malaria, but the pathophysiologic consequences have not been examined. It is induced by hemolysis, oxidative stress, and inflammation. It degrades heme, producing carbon monoxide (CO), which causes elevated levels of carboxyhemoglobin (COHb). In a prospective study of 1,520 children admitted to a Kenyan district hospital, COHb levels were no higher in children with malaria than with other infections. The COHb levels in children with severe malarial anemia were higher than in other children with malaria, but significantly lower than in children with other causes of severe anemia such as sickle cell disease. Levels of COHb were not significantly higher in children with cerebral malaria or in those dying of malaria. These results do not support a systemic increase in HO activity in malaria compared with other infectious diseases, but the roles of HO and CO in malaria require further study.

A retrospective cohort analysis was conducted in Kazakhstan to define modifiable risk factors during seven outbreaks of human anthrax. Fifty-three cases and 255 non-ill persons with an epidemiologic link to an infected animal were enrolled. Cases were 58% male and had a median age of 35 years (range = 5–71). Nearly all cases had cutaneous disease (96%). Two patients (4%) were diagnosed with gastrointestinal disease. Although all cases had some contact with an infected animal other than consumption, in multivariable analysis the act of butchering an animal (relative risk [RR] = 3.6, 95% confidence interval [CI] = 1.5–9.6) and the presence of visible cuts on the hands were associated with anthrax (RR = 3.0, 95% CI = 0.9–9.6). Contact with infected livestock, in particular butchering, is associated with developing anthrax. The risk may be exacerbated by the presence of cuts on the hands at the time of contact with the animal or animal products.

We report a case of a 56-year-old man with a history of splenectomy for idiopathic thrombocytopenic purpura who developed persistent bacteremia in the acute phase of human bartonellosis. This patient did not develop hemolytic anemia. Only after several courses of antibiotic treatment was the infection eradicated. This is an unusual case of overwhelming post-splenectomy infection by Bartonella bacilliformis, which provides clinical evidence that the spleen is a critical effector organ of clearance of this infection as well as the effector organ of bartonellosis-associated hemolytic anemia.

Shiqu County, located on the Tibetan plateau of western China, has an extremely high prevalence of both human alveolar echinococcosis (AE), and cystic echinococcosis (CE). The short form 12 version 2 quality of life survey, which was used to evaluate the extent to which morbidity associated with echinococcosis should be accounted, verified that there was a significant reduction in the mean health scores in all categories for individuals diagnosed with abdominal echinococcosis compared with an age and sex cross-matched population. Results of a larger ultrasound survey, which screened 3135 subjects, demonstrated that the prevalence rates of AE and CE were both approximately 6% with a combined prevalence rate of 11.4%. Prevalence rates adjusted for the age and sex structure of Shiqu County were 4.6% for AE and 4.9% for CE with an estimated overall adjusted prevalence rate of 9.5%. The burden of disease associated with echinococcosis was calculated using disability adjusted life years (DALYs) based on these estimated prevalence rates. Monte-Carlo techniques were used to model the uncertainty in the prevalence estimates and the disability weights. Using these methods, we estimated that the total numbers of DALYs lost due echinococcosis was 50,933 (95% confidence interval [CI] = 41,995–61,026). The DALYs lost consisted of approximately 32,978 (95% CI = 25,019–42,422) due to AE and 17,955 (95% CI = 14,268–22,128) due to CE and suggests an average of approximately 0.81 DALY lost per person. This study has clearly shown that the impact of DALYs lost due to echinococcosis, in terms of medical treatment costs, lost income, and physical and social suffering, is likely to be substantial in this highly endemic region of China.

The objective of this study was to assess the risk of infection with Giardia intestinalis in children living in an area with artificial groundwater recharge and potable water reuse in Mexico City. Eligible wells and surrounding homesteads were defined by using a geographic information system. Five wells were tested for G. intestinalis cysts per 400 liters of water. A total of 750 eligible households were visited during two cross-sectional surveys. Stool samples were provided by 986 children in the rainy season study and 928 children during the dry season survey for parasitologic tests. Their guardians provided information on water, sanitation, hygiene, and socioeconomic variables. The prevalence rates of G. intestinalis infection were 9.4% in the rainy season and 4.4% in the dry season. Higher rates of infection were observed in older individuals (9.5% and 10.6%) and girls had a lower risk of infection than boys (odds ratio [OR] =0.55, 95% confidence interval [CI] = 0.34, 0.88 in the rainy season and OR = 0.47, 95% CI = 0.25, 0.90 in the dry season). During the wet season survey, a health risk was detected among those storing water in unprotected receptacles (OR = 4.00, 4.69, and 5.34 for those using uncovered jars, cisterns or tanks, and buckets, respectively), and bathing outside the dwelling, i.e., using a tap (OR = 1.93, 95% CI = 1.10, 3.39). A health risk was also detected among children from households with unsafe food hygiene practices (OR =2.41, 95% CI =1.10, 5.30) and those with no hand-washing habits (OR = 2.27, 95% CI = 1.00, 5.20). Groundwater reserves are at risk of fecal pollution, as indicated by the presence of G. intestinalis cysts. However, the endemic pattern of intestinal infection reflects low standards of personal hygiene and unsafe drinking water storage and food-related practices at household level. Prevention activities must address health education and environmental protection policies.

Therapeutic failure in a human immunodeficiency virus-negative patient with visceral leishmaniasis was due to mixed infection by two different Leishmania infantum zymodemes: L. infantum zymodeme MON-98, which is a rare zymodeme and is reported for the first time in Greece, and zymodeme MON-1, which is common in the Mediterranean region. The two strains were isolated from two samples of bone marrow from the patient obtained before the administration of treatment and 20 days later, since there was no improvement in the clinical signs. The zymodemes MON-98 and MON-1 exhibited different behaviors in vitro and showed different sensitivities to meglumine antimoniate in vitro and in vivo, as shown by clinical findings. Mixed infections with different Leishmania strains may explain the differences in the clinical course of leishmaniasis in many patients and may be the reason for treatment failures.

This study analyzed genetic differentiation of 20 Aedes aegypti populations collected along a street in Phnom Penh Municipality of Cambodia. Using allozyme and microsatellite variations, we demonstrated that populations were differentiated and the pattern of differentiation was dependent on the type of breeding sites. Moreover, insecticide treatments with temephos mostly affect the population functioning of discarded containers. Low gene flow detected could limit the natural diffusion of resistant populations that might instead take advantage of human displacements to spread.

Since Paracoccidioides brasiliensis and Histoplasma capsulatum are known to be present in similar environments, there have been many epidemiologic investigations regarding the prevalences of these two organisms. However, cross-reactivity can occur in paracoccidioidin and histoplasmin skin tests, and this usually results in the overestimation of the prevalence of P. brasiliensis.The prevalence of infection with P. brasiliensis was evaluated in a cross-sectional study of 298 asymptomatic school children in the Brazilian Amazon region (Mato Grosso State). In this investigation, the reactivity of children to two different P. brasiliensis antigen preparations, paracoccidioidin and a purified 43-kD glycoprotein (gp43), was compared with or without the co-administration of histoplasmin. In the group of individuals receiving paracoccidioidin who had a positive histoplasmin skin test result, the prevalence of exposure to P. brasiliensis was 44% (16 of 36). This reactivity to P. brasiliensis was significantly higher than that observed in other groups, which ranged from 4% to 6% (P < 5 × 10−4 for each). Overall prevalence was 4.6% (95% confidence interval = 2.5–7.7%). These data suggest that gp43 provides a better estimate of exposure to P. brasiliensis when the co-administration of histoplasmin is desired.

The cysteine proteinases of Paragonimus westermani are known to play important roles in invasion and pathogenesis to hosts and in immune modulation and nutrient uptake. In this study, we have cloned a new cysteine proteinase of P. westermani, PwCP2, from adult worms and tested its diagnostic usefulness. The PwCP2 gene had an open reading frame of 816 base pairs and a conserved catalytic triad of cysteine, histidine, and asparagine residues. The mature form of recombinant PwCP2 (rPwCP2) lacking a proregion was overexpressed in Escherichia coli and used to produce antiserum. Western blot and immunohistochemical analyses using this antiserum showed that PwCP2 was expressed as a mature form, 24-kD product in a crude extract and in the excretory-secretory product of P. westermani, and was localized mainly in the intestinal epithelium of the adult worm. Western blot analysis using the rPwCP2 showed not only high sensitivity (90%) and specificity (100%) to sera from patients with paragonimiasis westermani, but also no cross-reactivity with sera from patients with clonorchiasis, sparganosis, or cysticercosis. Furthermore, an enzyme-linked immunosorbent assay using rPwCP2 exhibited a sensitivity of 93% and a specificity of 93% with sera of rats infected with P. westermani metacercariae. These results suggest that the excretory-secretory PwCP2 can be used for the diagnosis of paragonimiasis.

In serum samples obtained from all the healthy humans, horses, dogs, and donkeys present on three farms in the Pedreira Municipality, an endemic area for Brazilian spotted fever, an indirect immunofluorescence assay (IFA) detected antibodies against Rickettsia rickettsii in 17 (77.3%) horses, 5 (31.3%) dogs (titers ranging from 64 to 4,048), and none of 4 donkeys or 50 humans. Five canine and eight equine sera with high antibody titers to R. rickettsii were also tested by IFA against R. bellii, R. akari, and R. africae antigens. Sera from two horses and two dogs that showed similar high antibody titers against two rickettsial antigens were evaluated after cross-absorption. Sera from seven horses and two dogs contained antibodies specific for R. rickettsii, and one dog serum had antibodies against a Rickettsia species very closely related to R. africae. The latter may have been caused by infection with the recently identified COOPERI strain.

We aggregated published data from field studies documenting prevalence of Schistosoma haematobium infection and bladder pathology determined by ultrasonography or hematuria detected by reagent strip, questionnaire, or visual examination. A mathematical expression was used to describe the associations between prevalence of pathology/morbidity and infection. This allows for indirect comparison of these methods, which are rarely used simultaneously. All four methods showed a similar, marked association with infection. Surprisingly, ultrasound revealed higher prevalences of pathology in schools than in communities with the same prevalence of infection, implying a need for age-related cut-off values. Reagent strip testing yielded a higher prevalence than questionnaire, which in turn was higher than by visual examination. After correction for morbidity due to other causes, a consistent ratio in prevalence of hematuria of 3:2:1 resulted for the three respective methods. The simple questionnaire approach is not markedly inferior to the other techniques, making it the best option for field use.

It is difficult to completely eradicate strongyloidiasis, a human intestinal nematode infection with Strongyloides stercoralis with drugs, especially in males. To find host factors involved in the response to treatment, patients infected with S. stercoralis were examined for S. stercoralis-specific antibody titers and the effect of treatment with albendazole on these titers were determined. The cure rate was slightly but not significantly lower in males than in females (P = 0.108). However, a significantly higher titer of S. stercoralis-specific IgG4 antibody was observed in males than in females (P = 0.0097), and the S. stercoralis-specific IgG4 antibody titer was significantly higher in the male non-cured group than in the cured group (P = 0.035). These results suggest that elevation of the S. stercoralis-specific IgG4 antibody titer is associated with resistance to treatment of S. stercoralis infection, especially in males.

Culex pipiens was the dominant mosquito captured in a West Nile virus (WNV) focus in Stratford, Connecticut. More Cx. pipiens were captured in Centers for Disease Control miniature light traps baited with CO2, quail/hamster traps, and mosquito magnet experimental (MMX) traps placed in the tree canopy than in similar traps placed near the ground. Significantly more Cx. pipiens were captured in MMX traps placed in the canopy than in the other traps tested. Ninety-two percent and 85% of the 206 and 68 WNV isolations were from Cx. pipiens in 2002 and 2003, respectively; 5% and 12% were from Cx. salinarius. Eighty-five percent and 87% of the isolates were from mosquitoes captured in the canopy in each of the two years. The significantly larger numbers of WNV isolates from Cx. pipiens captured in the canopy are attributed to the significantly larger numbers of Cx. pipiens captured in the canopy in comparison to those captured in traps near the ground.