Chronic type 2 reaction in lepromatous leprosy with underlying Plasmodium falciparum infection: A case report.

Tropical diseases prevalent in leprosy-endemic areas may alter the immunological patient response and also complicate the presentation of leprosy reactional episodes. The introduction of anti-malarial drugs in our case produced a subsidence of reaction. With dwindling manpower skilled in leprosy, the reactional episodes are very often treated with non-steroidal anti-inflammatory drugs, steroids and thalidomide, neglecting the possibility of other co-existing infections, tropical or other. Our case emphasises the importance of history, examination and balanced investigation in the context of tropical diseases in endemic areas before injudicious intervention.

Environmental modifiers of RTS,S/AS01 malaria vaccine efficacy in Lilongwe, Malawi.

BACKGROUND: RTS,S/AS01 is the first vaccine against malaria to undergo pilot implementation, beginning in 2019 and vaccinating 360,000 children per year in Malawi, Ghana, and Kenya. The four-dose vaccine is given as a primary three-dose series with a fourth dose given approximately 18 months later. The efficacy of RTS,S/AS01 was variable among the 11 sites participating in the 2009-2014 phase III trial (MALARIA-055, NCT00866619), possibly due to differences in transmission intensity. However, a within-site examination of environmental factors related to transmission intensity and their impact on vaccine efficacy has yet to be conducted. METHODS: We implemented the phase III RTS,S/AS01 trial at the Malawi site, which enrolled 1578 infants (6-12 weeks) and children (5-17 months) living in the Lilongwe District in Central Malawi and followed them for 3 years between 2009 and 2014. A global positioning system survey and an ecological questionnaire were conducted to collect participant household locations and characteristics, while additional data on background malaria prevalence were obtained from a concurrent Malaria Transmission Intensity (MTI) survey. Negative binomial regression models were used to assess whether the efficacy of the vaccine varied by estimated background malaria prevalence, household roof type, or amount of nearby vegetation. RESULTS: Vaccine efficacy did not significantly vary by estimated malaria prevalence or by roof type. However, increased vegetation cover was associated with an increase in the efficacy of the three-dose primary RTS,S/AS01 series in the 18 months before the fourth dose and a decrease in the efficacy of the primary vaccine series in the second 18 months following, if the fourth dose was not given. Vegetation cover did not alter the efficacy of the fourth dose in a statistically or practically significant manner. CONCLUSIONS: Vegetation coverage in this study site might be a proxy for nearness to rivers or branching, shallow wetlands called "dambos" which could serve as breeding sites for mosquitoes. We observed statistically significant modification of the efficacy of RTS,S/AS01 by forest cover, suggesting that initial vaccine efficacy and the importance of the fourth dose varies based on ecological context. TRIAL REGISTRATION: Efficacy of GSK Biologicals' Candidate Malaria Vaccine (257049) Against Malaria Disease Caused by P. falciparum Infection in Infants and Children in Africa. NCT00866619 prospectively registered 20 March 2009.

Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo.

The present study evaluated the growth-inhibitory effects of clofazimine, currently used for treating leprosy, against Babesia bovis, B. bigemina, B. caballi, and Theileria equi in in vitro culture and against Babesia microti in mice. The 50% inhibitory concentrations (IC50s) of clofazimine against the in vitro growth of B. bovis, B. bigemina, B. caballi, and T. equi were 4.5, 3, 4.3, and 0.29 µM, respectively. In mice infected with B. microti, treatment with 20 mg/kg of body weight of clofazimine administered orally resulted in a significantly lower peak parasitemia (5.3%) than that in the control group (45.9%), which was comparable to the subcutaneous administration of 25 mg/kg diminazene aceturate, the most widely used treatment for animal piroplasmosis. Although slight anemia was observed in both clofazimine- and diminazene aceturate-treated infected mice, the level and duration of anemia were lower and shorter, respectively, than those in untreated infected mice. Using blood transfusions and PCR, we also examined whether clofazimine completely killed B. microti On day 40 postinfection, when blood analysis was performed, parasites were not found in blood smears; however, the DNA of B. microti was detected in the blood of clofazimine-treated animals and in several tissues of clofazimine- and diminazene aceturate-treated mice by PCR. The growth of parasites was observed in mice after blood transfusions from clofazimine-treated mice. In conclusion, clofazimine showed excellent inhibitory effects against Babesia and Theileria in vitro and in vivo, and further study on clofazimine is required for the future development of a novel chemotherapy with high efficacy and safety against animal piroplasmosis and, possibly, human babesiosis.

Biology-based mapping of vector-borne parasites by geographic information systems and remote sensing.

Application of growing degree day-water budget analysis and satellite climatology to vector-borne parasites will be reviewed to demonstrate the value of using the unique thermal-hydrological preferences and limits of tolerance of individual parasite-vector systems to define the environmental niche of disease agents in the landscape by modern geospatial analysis methods. Applications of geospatial modeling will be illustrated by examples on fascioliasis, malaria, leprosy and leishmaniasis.

Specific killing of cytotoxic T cells and antigen-presenting cells by CD4+ cytotoxic T cell clones. A novel potentially immunoregulatory T-T cell interaction in man.

Mycobacterial antigens not only stimulate Th cells that produce macrophage-activating factors, but also CD4+ and CD8+ CTL that lyse human macrophages. The mycobacterial recombinant 65-kD hsp was previously found to be an important target antigen for polyclonal CD4+ CTL. Because of the major role of 65-kD hsp in the immune response to mycobacterial as well as autoantigens, we have studied CTL activity to this protein at the clonal level. HLA-DR or HLA-DQ restricted, CD4+CD8- T cell clones that recognize different peptides of the M. leprae 65-kD hsp strongly lysed EBV-BLCL pulsed with specific but not irrelevant peptide. No bystander lysis of B cells, T cells, or tumor cells was seen. Target cell lysis could not be triggered by PMA + Ca2+ ionophore alone and depended on active metabolism. Interestingly, these CD4+ CTL also strongly lysed themselves and other HLA-class II compatible CD4+ (TCR-alpha/beta or -gamma/delta) or CD8+ CTL clones in the presence of peptide, suggesting that CTL are not actively protected from CTL-mediated lysis. Cold target competition experiments suggested that EBV-BLCL targets were more efficiently recognized than CD4+ CTL targets. These results demonstrate that hsp65 peptide-specific HLA class II-restricted CD4+ T cell clones display strong peptide-dependent cytolytic activity towards both APCs, and, unexpectedly, CD4+ and CD8+ CTL clones, including themselves. Since, in contrast to murine T cells human T cells express class II, CTL-mediated T cell killing may represent a novel immunoregulatory pathway in man.

Public-health epidemiology in Vanuatu.

Vanuatu, which formerly was known as the New Hebrides, is an archipelago in the southwest Pacific Ocean with a tropical humid climate. The national health system and the state of health of the population generally are satisfactory. The main diseases of public-health importance are malaria and tuberculosis. Their epidemiology and control are discussed. An epidemic of Plasmodium falciparum malaria, which commenced in 1980, is described; this possibly can be explained by an increase in chloroquine-resistant P. falciparum over the same period. Other diseases also are reviewed. Many tropical diseases of great significance elsewhere are not of much significance in Vanuatu. Medical advice for visiting travellers is provided.

Public-health epidemiology in Vanuatu

Vanuatu, which formerly was known as the New Hebrides, is an archipelago in the southwest Pacific Ocean with a tropical humid climate. The national health system and the state of health of the population generally are satisfactory. The main diseases of public-health importance are malaria and tuberculosis. Their epidemiology and control are discussed. An epidemic of Plasmodium falciparum malaria, which commenced in 1980, is described; this possibly can be explained by an increase in chloroquine-resistant P. falciparum over the same period. Other diseases also are reviewed. Many tropical diseases of great significance elsewhere are not of much significance in Vanuatu. Medical advice for visiting travellers is provided.

Comparison between autoantibodies in malaria and leprosy with lupus.

Sera from 16 patients with falciparum malaria, 16 patients with vivax malaria and 31 patients with leprosy were tested for autoantibodies to intracellular proteins and nucleic acids. Precipitating antibodies to soluble protein extracts were not detected in any serum. Sera from malaria patients showed prominent immunofluorescence staining of the HEP2 nuclear membrane as well as frequent 75% (24/32) and intense Western blot reactivity. In contrast, only 20% and 36% of patients with leprosy had positive immunofluorescence or positive immunoblots respectively, and reactivity was weak in most cases. Neither the malaria nor leprosy sera contained autoantibodies with specificities similar to the characteristic lupus autoantibodies such as double stranded DNA (dsDNA), Ro/SSA, La/SSB, Sm, RNP and P proteins. Low levels of antibodies to single stranded (ssDNA) were however found in 11 (34%) malaria sera and in seven (23%) leprosy sera. Thirteen percent of patients with leprosy had anti-histone antibodies. These findings demonstrate considerable differences in the capacity of infectious agents to induce autoantibodies and also the infrequency with which autoantibodies characteristic of idiopathic systemic lupus erythematosus are induced.

The malaria burden and population growth in the Solomon Islands.

This paper outlines the result of the control of infectious diseases, and more especially malaria, on the growth of populations in the Solomon Islands since 1931, the year of the first census, to 1976, the year in which the fourth census revealed, that a population explosion had occurred, and was occurring unabated.

PIP: The result of the control of infectious diseases, and particularly malaria, on the growth of populations in the Solomon Islands over the 1931-1976 period is outlined. The 1976 4th census revealed that a population explosion had occurred and was occurring unabated. The greatest population increase was during the 1970-1976 period, when the population rose from 160,998 to 196,708, representing an annual rate of growth of 3.4% per annum. The primary reason for this dramatic population increase is the control of infectious diseases, and to the control of malaria in particular. The control of malaria was most marked since total coverage with insecticide spraying was achieved in early 1972, following the initiation of the Malaria Eradication Program. Along with the attacks on the endemic diseases, there has been a progressive improvement in the coverage and care provided by the basic Health Services. The assessment of a Malaria Eradication Program is carried out by the determination of the Annual Parasite Incidence or API which must be based on full surveillance activities, and the Annual Blood Examination Rate.