Association of house spraying with suppressed levels of drug resistance in Zimbabwe

BACKGROUND: Public health strategies are needed to curb antimalarial drug resistance. Theoretical argument points to an association between malaria transmission and drug resistance although field evidence remains limited. Field observations, made in Zimbabwe, on the relationship between transmission and multigenic drug resistance, typified by chloroquine, are reported here. METHODS: Periodic assessments of the therapeutic response of uncomplicated falciparum malaria to chloroquine in two selectively sprayed or unsprayed health centre catchments, from 1995 – 2003. Cross-sectional analysis of in vivo chloroquine failure events for five sites in relation to natural endemicity and spraying history. RESULTS: During selective house spraying, the chloroquine failure rate for the sprayed catchment decreased, such that, after four years, the odds of chloroquine failure were 4× lower than before start of spraying in the area (OR 0.2, 95% CI 0.07 – 0.75, p = 0.010, n = 100). Chloroquine failure odds for the sprayed area became 4× lower than contemporaneous failure odds for the unsprayed area (OR 0.2 95% CI 0.08 – 0.65, p = 0.003, n = 156), although the likelihood of failure was not significantly different for the two catchments before selective spraying started (OR 0.5, 95% CI 0.21 – 1.32; p = 0.170, n = 88). When spraying ended, in 1999, the drug failure odds for the former sprayed area increased back 4 fold by 2003 (OR 4.2, 95%CI 1.49 – 11.78, p = 0.004, n = 146). High altitude areas with naturally lower transmission exhibited a 6× lower likelihood of drug failure than low-lying areas (OR 0.16 95% CI 0.068 – 0.353, -2 log likelihood change 23.239, p < 0.001, n = 465). Compared to sites under ongoing annual spraying, areas that were last sprayed 3–7 years ago experienced a 4-fold higher probability of chloroquine failure (OR 4.1, 95%CI 1.84 – 9.14, -2 log likelihood change 13.956, p < 0.001). CONCLUSION: Reduced transmission is associated with suppressed levels of resistance to chloroquine and presumably other regimens with multigenic drug resistance. It seems the adoption of transmission control alongside combination chemotherapy is a potent strategy for the future containment of drug-resistant malaria

Changes in the Burden of Malaria Following Scale up of Malaria Control Interventions in Mutasa District, Zimbabwe

Background: To better understand trends in the burden of malaria and their temporal relationship to control activities, a survey was conducted to assess reported cases of malaria and malaria control activities in Mutasa District, Zimbabwe. Methods: Data on reported malaria cases were abstracted from available records at all three district hospitals, three rural hospitals and 25 rural health clinics in Mutasa District from 2003 to 2011. Results: Malaria control interventions were scaled up through the support of the Roll Back Malaria Partnership, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and The President\u27s Malaria Initiative. The recommended first-line treatment regimen changed from chloroquine or a combination of chloroquine plus sulphadoxine/ pyrimethamine to artemisinin-based combination therapy, the latter adopted by 70%, 95% and 100% of health clinics by 2008, 2009 and 2010, respectively. Diagnostic capacity improved, with rapid diagnostic tests (RDTs) available in all health clinics by 2008. Vector control consisted of indoor residual spraying and distribution of longlasting insecticidal nets. The number of reported malaria cases initially increased from levels in 2003 to a peak in 2008 but then declined 39% from 2008 to 2010. The proportion of suspected cases of malaria in older children and adults remained high, ranging from 75% to 80%. From 2008 to 2010, the number of RDT positive cases of malaria decreased 35% but the decrease was greater for children younger than five years of age (60%) compared to older children and adults (26%). Conclusions: The burden of malaria in Mutasa District decreased following the scale up of malaria control interventions. However, the persistent high number of cases in older children and adults highlights the need for strategies to identify locally effective control measures that target all age groups

Distribution of schistosomiasis and soil transmitted Helminthiasis in Zimbabwe:Towards a national plan of action for control and elimination

Schistosomiasis and STH are among the list of neglected tropical diseases considered for control by the WHO. Although both diseases are endemic in Zimbabwe, no nationwide control interventions have been implemented. For this reason in 2009 the Zimbabwe Ministry of Health and Child Care included the two diseases in the 2009-2013 National Health Strategy highlighting the importance of understanding the distribution and burden of the diseases as a prerequisite for elimination interventions. It is against this background that a national survey was conducted.A countrywide cross-sectional survey was carried out in 280 primary schools in 68 districts between September 2010 and August 2011. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni and STH (hookworms, Trichuris trichiura, Ascaris lumbricoides) were diagnosed using both the Kato Katz and formol ether concentration techniques.Schistosomiasis was more prevalent country-wide (22.7%) than STH (5.5%). The prevalence of S. haematobium was 18.0% while that of S. mansoni was 7.2%. Hookworms were the most common STH with a prevalence of 3.2% followed by A. lumbricoides and T. trichiura with prevalence of 2.5% and 0.1%, respectively. The prevalence of heavy infection intensity as defined by WHO for any schistosome species was 5.8% (range 0%-18.3% in districts). Only light to moderate infection intensities were observed for STH species. The distribution of schistosomiasis and STH varied significantly between provinces, districts and schools (p<0.001). Overall, the prevalence of co-infection with schistosomiasis and STH was 1.5%. The actual co-endemicity of schistosomiasis and STH was observed in 43 (63.2%) of the 68 districts screened.This study provided comprehensive baseline data on the distribution of schistosomiasis and STH that formed the basis for initiating a national control and elimination programme for these two neglected tropical diseases in Zimbabwe

Seroepidemiology of Plasmodium falciparum, human immunodeficiency virus and human T-cell leukemia virus infections in mothers and their infants in Zimbabwe

Thesis (Ph. D.)--University of Hawaii at Manoa, 1995.Includes bibliographical references (leaves 108-129).Microfiche.xi, 129 leaves, bound ill., maps, photos. 29 cmMatched blood samples from parturients and their neonates were screened for malaria parasites and analyzed for P. falciparum immunoglobulin G (IgG), IgM, IgE, human immunodeficiency virus-1 (HIV-1) and human T-cell leukemia viruses-I/II (HTLV-I/II) by enzyme-linked immunosorbent assay (ELISA) and Western immunoblot. Three paired sera were positive for P. falciparum parasites, and the ELISA positivity rates for P. falciparum IgG, IgM, and IgE antibodies for maternal sera were 50.2%, 91.2% and 22.7%, respectively whereas those for cord sera were 24.9%, 14.9% and 2.7%, respectively. Overall cord antibody positivity rates were independent of maternal antibodies. P. falciparum IgG antibody rates by ELISA were not influenced by parity for parities 1 to 6 or greater but were related to parity when parity was grouped into parity 1 and 2 or greater. IgG antibody production was not significantly related to maternal age. P. falciparum IgG, IgM and IgE antibody positivity rates by immunoblot were 78.1%, 39.6% and 1.33% for maternal sera and 72.5%, 14.3% and 1.33% for cord sera, respectively. Matched maternal and cord sera with very strong to strong IgG immunoblot reactivities showed near homology for each pair. The most prevalent and strong antigen complexes in the positive IgG immunoblots were 195- to 170-, 91- to 75- and 48-kDa. There was no homology for each pair in the immunoblots of P. falciparum IgM antibody positive sera. The antigen complexes that were most frequent and strongly recognized by IgM immunoblot positive sera were 91- to 75and 21-kDa. P. falciparum IgM and IgG antibodies were copositive in 33% of the maternal sera tested by immunoblot. The HIV-1 seropositivity rates for maternal sera were 48.7% and 34.9% by ELISA and Western blot respectively. Women aged 31 to 35 years had the highest rates of HIV-1 infection. The positivity rates for HTLV-I/II in the parturients were 87% by ELISA and either negative (48.4%) or indeterminate (56.2%) by Western immunoblot for HTLV-I/II antigen, suggesting possible early infection with the viruses. P. falciparum IgG antibody reactivity with parasite antigen was observed in 49.1% and 91.7% of matched pairs that were HIV-1 IgG positive and HIV-1 IgG negative respectively in immunoblot assays. Less bands of lower intensity were formed on immunoblots of the former than the latter. These differences in reactivities were highly significant (z=3.97, p<0.00) and suggestive of P. falciparum IgG antibody immunosuppression by HIV-1 infection

High prevalence of molecular markers for resistance to chloroquine and pyrimethamine in Plasmodium falciparum from Zimbabwe

Chloroquine has been the first line drug of treatment for malaria in Zimbabwe until a recent adoption of an interim policy to treat using a combination of chloroquine (CQ) and sulfadoxine/pyrimethamine (SP). We examined the prevalence of parasites with mutations associated with resistance to the drug combination in three areas that have been previously described to differ in malaria endemicity. Our results show that the parasite population from the three areas had a high prevalence of molecular markers of resistance to chloroquine and pyrimethamine. The prevalence of crt (K76T) was 64, 82, and 92% for Chiredzi, Kariba, and Bindura, respectively. On the dhfr locus, the presence of triple mutations (codons 51, 59, and 108) was approximately 50% for all the three locations. On the other hand, the prevalence of dhps mutations (codons 436, 437, and 540) was low accounting for less than 20% in all the areas. Studies reported here demonstrate widespread prevalence of molecular markers associated with chloroquine and pyrimethamine resistance and should be taken into consideration for further refinement of malaria control strategies in Zimbabwe. The design and implementation of successful control strategies would benefit from understanding the prevalence of mutations associated with drug resistance in parasite populations. © 2007 Springer-Verlag

Analysis of TNF-a and IL-10 gene polymorphisms in Zimbabwean children exposed to malaria

Single nucleotide polymorphisms within the cytokine genes, TNF-α (-308 G/A), and IL-10 (-1082 A /G and -819 T/C) associated with protection and susceptibility to parasitic infections were examined in samples from school aged children in the Eastern district of Zimbabwe. Whole blood specimens were obtained from 491 children between the ages of 5 – 16 years, of which 26.9% were infected with Plasmodium falciparum and 73.1% were not infected. Genotyping was carried out using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The prevalence of TNF-α genotypes GG, GA and AA associated with low, intermediate and high cytokine production was 80, 19 and 2%, respectively. Wild type alleles TNF-α -308G* predominated in both infected and uninfected individuals in the study. For IL-10 (position -819) the distribution of wild-type alleles CC*, heterozygotes and mutant carriers TT* was 64, 27 and 9%, respectively, and a similar analysis of the polymorphisms on position -1082 for IL-10 revealed that most of the samples were heterozygotes (95%). There was no statistically significant difference in the frequencies of polymorphisms on TNF-α (-308G/A) (X2 = 1.820; p = 0.403), IL-10 (-1082 A/G) (X2 = 0.242; p = 0.623) and IL-10 (-819C/T) among children infected with P. falciparum and those without infection. Finally, the high prevalence of heterozygotes would suggest moderate to high IL-10 responses in the population analyzed and that an anti-inflammatory environment dominates when faced with acute P. falciparum infection in the samples analyzed.Keywords: Polymorphism, cytokines, Plasmodium falciparum, malariaAfrican Journal of Biotechnology Vol. 12(10), pp. 1034-1039, 6 March, 201

Antibody responses to Plasmodium falciparum vaccine candidate antigens in three areas distinct with respect to altitude.

Antibody levels against malaria antigens were measured among patients presenting with uncomplicated malaria at health centers from three locations in Zimbabwe (Bindura, Chiredzi and Kariba) that are distinct with regard to altitude and climatic conditions. Antibody levels were determined by ELISA using the antigens, apical membrane antigen 1 (AMA-1), erythrocyte binding antigen 175 (EBA-175), circumsporozoite surface protein (CSP), merozoite surface protein 1 (MSP-1) and Pfg27. For all the antigens tested, IgG and IgM levels were higher for Bindura (altitude 1100 m) compared to Kariba (<600 m, altitude) and Chiredzi (approximately 600 m, altitude) with the exception of IgG and IgM to AMA-1 and EBA-175 which were similar between Chiredzi and Bindura. Plasma samples were further analyzed for their functional activity by testing their ability to inhibit the growth of Plasmodium falciparum in culture. Our results, determined by microscopy and verified by the LDH assay revealed that plasma from the three locations had similar inhibitory activity against the growth of P. falciparum in vitro. Our data revealed that highest growth inhibition correlated with the highest levels of MSP-1 antibody values